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1.  Most women diagnosed with cervical cancer by a visual screening program in Tanzania completed treatment: evidence from a retrospective cohort study 
BMC Public Health  2014;14(1):910.
Background
Visual inspection with acetic acid (VIA) to identify and treat pre-cancerous lesions is effective for cervical cancer prevention. Screening programs also facilitate screening and diagnosis of invasive cancers that must be referred for radiation therapy or chemotherapy. This study compared characteristics of women diagnosed with invasive cervical cancer by a VIA screening program who did and did not follow up for treatment and who did and did not complete treatment at the Ocean Road Cancer Institute (ORCI), Dar es Salaam, Tanzania.
Methods
We conducted a retrospective cohort study of ORCI screening referrals from the period November 2002 to June 2011. Women referred for treatment of invasive disease (n = 980) were identified from an existing database of all women attending the screening clinic during this period (n = 20,131) and matched to a dataset of all cervical cancer patients attending ORCI in this period (n = 8,240). Treatment information was abstracted from patient records of women who followed up. Records of a random sample (n = 333) of unscreened patients were reviewed for disease stage.
Results
Of the 980 women referred women, 829 (84.6%) sought treatment. Most of those women (82.8%) completed their prescribed radiation. Lower disease stage, having a skilled occupation, residence in Dar es Salaam, and younger age were independently associated with loss to follow-up. Higher disease stage, residence in Dar es Salaam, older age, and later year of first treatment appointment were independently associated with incomplete treatment among those who followed up. Significantly more screened women had stage 1 disease (14.0%) than unscreened women (7.8%).
Conclusions
Most women referred from the screening clinic completed treatment for their cancer at ORCI. Some of those lost to follow-up may have sought treatment elsewhere. In most cases, the screening clinic appears to facilitate diagnosis and treatment, rather than screening, for women with invasive cervical cancer.
doi:10.1186/1471-2458-14-910
PMCID: PMC4162936  PMID: 25187329
Cervical cancer; Screening; Visual inspection with acetic acid; Referral patterns; Radiation therapy; Tanzania
2.  Cervical Screening at Age 50–64 Years and the Risk of Cervical Cancer at Age 65 Years and Older: Population-Based Case Control Study 
PLoS Medicine  2014;11(1):e1001585.
Peter Sasieni and colleagues use a population-based case control study to assess the risk of cervical cancer in screened women aged over 65 years to help inform policy on the upper age of cervical cancer screening.
Please see later in the article for the Editors' Summary
Background
There is little consensus, and minimal evidence, regarding the age at which to stop cervical screening. We studied the association between screening at age 50–64 y and cervical cancer at age 65–83 y.
Methods and Findings
Cases were women (n = 1,341) diagnosed with cervical cancer at age 65–83 y between 1 April 2007 and 31 March 2012 in England and Wales; age-matched controls (n = 2,646) were randomly selected from population registers. Screening details from 1988 onwards were extracted from national databases. We calculated the odds ratios (OR) for different screening histories and subsequent cervical cancer. Women with adequate negative screening at age 65 y (288 cases, 1,395 controls) were at lowest risk of cervical cancer (20-y risk: 8 cancers per 10,000 women) compared with those (532 cases, 429 controls) not screened at age 50–64 y (20-y risk: 49 cancers per 10,000 women, with OR = 0.16, 95% CI 0.13–0.19). ORs depended on the age mix of women because of the weakening association with time since last screen: OR = 0.11, 95% CI 0.08–0.14 at 2.5 to 7.5 y since last screen; OR = 0.27, 95% CI 0.20–0.36 at 12.5 to 17.5 y since last screen. Screening at least every 5.5 y between the ages 50 and 64 y was associated with a 75% lower risk of cervical cancer between the ages 65 and 79 y (OR = 0.25, 95% CI 0.21–0.30), and the attributable risk was such that in the absence of screening, cervical cancer rates in women aged 65+ would have been 2.4 (95% CI 2.1–2.7) times higher. In women aged 80–83 y the association was weaker (OR = 0.49, 95% CI 0.28–0.83) than in those aged 65–69 y (OR = 0.12, 95% CI 0.09–0.17). This study was limited by an absence of data on confounding factors; additionally, findings based on cytology may not generalise to human papillomavirus testing.
Conclusions
Women with adequate negative screening at age 50–64 y had one-sixth of the risk of cervical cancer at age 65–83 y compared with women who were not screened. Stopping screening between ages 60 and 69 y in women with adequate negative screening seems sensible, but further screening may be justifiable as life expectancy increases.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Nearly one in ten cancers diagnosed in women occur in the cervix, the structure that connects the womb to the vagina. Every year, more than a quarter of a million women (mostly in developing countries) die because of cervical cancer, which occurs only after the cervix has been infected with human papillomavirus (HPV) through sexual intercourse. In the earliest stages of cervical cancer, abnormal cells begin to grow in the cervix. Cells with low-grade abnormalities (changes that often revert to normal), cells with high-grade abnormalities (which are more likely to become cancerous), and cancer cells can all be detected by collecting a few cells from the cervix and examining them under a microscope. This test forms the basis of cervical screening, which has greatly reduced cervical cancer deaths in countries with a national screening program by ensuring that cervical abnormalities are detected at an early, treatable stage. In the UK, for example, since the start of a cervical screening program in 1988 in which women aged 25–64 years are called for testing every 3–5 years, the incidence of cervical cancer (the number of new cases per year) has almost halved at a time when sexually transmitted diseases have more than doubled.
Why Was This Study Done?
Currently, there is little consensus about the age at which cervical screening should stop, and minimal evidence about the impact of cervical screening on the incidence of cervical cancer in older women. In this population-based case control study (a study that compares the characteristics of all the cases of a disease in a population with the characteristics of matched individuals without the disease), the researchers examine the association between screening in women aged 50–64 years and cervical cancer in women aged 65–83 years. They ask whether well-screened women with a history of negative results and no evidence of high-grade abnormalities are at sufficiently low risk of cervical cancer that screening can be stopped at age 65 years, and whether women who are regularly screened (at least once every 5.5 years) between the ages of 50 and 64 years are subsequently at reduced risk of cervical cancer.
What Did the Researchers Do and Find?
The researchers randomly selected two age-matched controls for every woman aged 65–83 years who was diagnosed with cervical cancer between 2007 and 2012 in England and Wales. The researchers included 1,341 women with cervical cancer and 2,646 controls. They extracted each woman's cervical screening details from national databases and calculated the association between screening history and subsequent cervical cancer. Women with adequate negative screening at age 65 years (at least three tests at age 50–64 years with the last one over age 60, the last three of which were negative, and no evidence of high-grade abnormalities) were at the lowest risk of cervical cancer (20-year risk of eight cancers per 10,000 women) compared with unscreened women (20-year risk of 49 cancers per 10,000 women). That is, women who were not screened at age 50–64 years were six times more likely to develop cervical cancer between the ages of 65 and 83 years than women who were screened. The risk of developing cervical cancer among adequately negatively screened women increased with age and with time since the last screen. Finally, the researchers estimate that in the absence of any cervical screening, the rate of cervical cancer among women aged 65–79 years would be 23 cases per 100,000 woman-years, 2.4 times higher than the current rate.
What Do These Findings Mean?
These findings show that women who exited the screening program in England and Wales with a history of adequate negative screening between the ages of 50 and 64 years were at a very low risk of being diagnosed with cervical cancer at the age of 65 years or older. The “protection” provided by screening was greatest for women aged 65–69 years and decreased steadily with increasing age and with time since the last negative screen. Because the researchers did not have any information on other characteristics that might have affected cervical cancer risk (for example, number of sexual partners), the women who were screened may have shared other characteristics that reduced their risk of developing cervical cancer. Moreover, these findings, which are based on microscopic examination of cells, may not generalise to the HPV-based screening programs that many countries are considering. Despite these limitations, the researchers conclude that, for now, it seems sensible to continue screening at least until age 60 years and not beyond age 69 years in women with adequate negative screening, but that given increasing life expectancy, screening in older women might be justified in the future.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001585.
This study is further discussed in a PLOS Medicine Perspective by Anne Rositch and colleagues
The US National Cancer Institute provides information about cervical cancer for patients and for health professionals, including information on cervical screening (in English and Spanish)
The US Centers for Disease Control and Prevention also has information about cervical cancer and about cervical screening
The UK National Health Service Cervical Screening Programme website has detailed information and statistics on cervical screening in England
The UK National Health Service Choices website has pages on cervical cancer (including a personal story about cervical cancer) and on cervical screening (including personal comments about screening)
Cancer Research UK provides detailed information about all aspects of cervical cancer
More information about cervical cancer and screening is available from the Macmillan cancer charity
MedlinePlus provides links to additional resources about cervical cancer and screening (in English and Spanish)
Personal stories about cervical cancer and about cervical screening are available through the charity Healthtalkonline
doi:10.1371/journal.pmed.1001585
PMCID: PMC3891624  PMID: 24453946
3.  Demographic, knowledge, attitudinal, and accessibility factors associated with uptake of cervical cancer screening among women in a rural district of Tanzania: Three public policy implications 
BMC Public Health  2012;12:22.
Background
Cervical cancer is an important public health problem worldwide, which comprises approximately 12% of all cancers in women. In Tanzania, the estimated incidence rate is 30 to 40 per 100,000 women, indicating a high disease burden. Cervical cancer screening is acknowledged as currently the most effective approach for cervical cancer control, and it is associated with reduced incidence and mortality from the disease. The aim of the study was to identify the most important factors related to the uptake of cervical cancer screening among women in a rural district of Tanzania.
Methods
A cross sectional study was conducted with a sample of 354 women aged 18 to 69 years residing in Moshi Rural District. A multistage sampling technique was used to randomly select eligible women. A one-hour interview was conducted with each woman in her home. The 17 questions were modified from similar questions used in previous research.
Results
Less than one quarter (22.6%) of the participants had obtained cervical cancer screening. The following characteristics, when examined separately in relation to the uptake of cervical cancer screening service, were significant: husband approval of cervical cancer screening, women's level of education, women's knowledge of cervical cancer and its prevention, women's concerns about embarrassment and pain of screening, women's preference for the sex of health provider, and women's awareness of and distance to cervical cancer screening services. When examined simultaneously in a logistic regression, we found that only knowledge of cervical cancer and its prevention (OR = 8.90, 95%CI = 2.14-16.03) and distance to the facility which provides cervical cancer screening (OR = 3.98, 95%CI = 0.18-5.10) were significantly associated with screening uptake.
Conclusions
Based on the study findings, three recommendations are made. First, information about cervical cancer must be presented to women. Second, public education of the disease must include specific information on how to prevent it as well as screening services available. Third, it is important to provide cervical cancer screening services within 5 km of where women reside.
doi:10.1186/1471-2458-12-22
PMCID: PMC3299640  PMID: 22233530
Public health; Policy; Cervical cancer screening; Women's health
4.  Health-related quality of life and needs of care and support of adult Tanzanians with cancer: a mixed-methods study 
Background
Cancer is among the three leading causes of death in low income countries and the highest increase with regard to incidence figures for cancer diseases are found in these countries. This is the first report of the health-related quality of life (HRQOL) and needs of care and support of adult Tanzanians with cancer.
Methods
A mixed-methods design was used. The study was conducted at Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania. One hundred and one patients with a variety of cancer diagnoses treated and cared for at ORCI answered the Kiswahili version of the EORTC QLQ-C30 investigating HRQOL. Thirty-two of the patients participated in focus group interviews discussing needs of care and support. Data from focus group interviews were analyzed with content analysis.
Results
The findings show that the patients, both women and men, report a low quality of life, especially with regard to physical, role, and social function and a high level of symptoms and problems especially with financial difficulties and pain. Financial difficulties are reported to a remarkably high extent by both women and men. The patients, both women and men report least problems with emotional function. A content analysis of the interview data revealed needs of food and water, hygienic needs, emotional needs, spiritual needs, financial needs, and needs of closeness to cancer care and treatment services.
Conclusion
The high score for pain points out that ORCI is facing severe challenges regarding care and treatment. However, when considering this finding it should be noted that the pain subscale of the Kiswahili version of the EORTC QLQ-C30 did not reach acceptable internal consistency and showed less than satisfactory convergent validity. This also applies to the subscales cognitive function and global health/quality of life. Attention should be drawn to meet the identified needs of Tanzanian cancer patients while hospitalized but also when at home. Increased accessibility of mosquito nets, pads, and pain-killers would help to fulfil some needs.
doi:10.1186/1477-7525-10-133
PMCID: PMC3541157  PMID: 23121718
Cancer; Care; Health-related quality of life; Support; Tanzania
5.  Clinical and Epidemiologic Profile of Breast Cancer in Tanzania 
Breast disease  2010;31(1):33-41.
Purpose
Breast cancer is a highly heterogeneous disease globally. Public health prevention measures require an understanding of the burden of breast cancer and its risk factors. The purpose of this study was to describe the clinical, pathologic, and epidemiologic characteristics of breast cancer patients in Tanzania.
Methods
Data was abstracted from the medical records of all breast cancer patients attending Ocean Road Cancer Institute (ORCI) over a 2-year period from July 2007 to June 2009. Tumor tissue paraffin blocks were collected for all patients with available tissues for the determination of estrogen receptor (ER) and progesterone receptor (PR). Data for all patients was analyzed descriptively and by using unconditional logistic regression, by comparing early stage (ES), defined as stages I and II and late stage (LS), defined as stages III and IV patients to obtain odds ratios (ORs), 95% confidence intervals (CIs), and P -values.
Results
Among the 488 patients, stage was determined for 356 patients, 90.7% of whom presented in LS. Of the 57 tumor tissues, 49.1% were ER−/PR−. Patients with ulceration (OR = 4.97; 95% CI = 1.07, 23.04; p = 0.04) and peau d’orange (OR = 6.78; 95% CI = 1.48, 31.17; p = 0.01) were more likely to present in LS rather than ES. Male breast cancer accounted for 2.9% of all breast cancers and inflammatory breast cancer (IBC) comprised 4.3–5.5% of cases based on registered t4d diagnosis or the criteria of IBC signs, if t4d was not reported in the medical records.
Conclusion
Most breast cancer patients in Tanzania are diagnosed at advanced disease stages with about half of the tumors being ER−/PR−. These data strongly support that reducing barriers to care, down-staging of disease at diagnosis, implementation of clinical guidelines for management of advanced cases, and palliative care are the four most essential factors that need to be addressed to reduce morbidity and mortality from breast cancer in Tanzania. Further research is needed to quantify the magnitude and molecular features of two relatively rare forms of breast cancer that may account for a greater proportion of the burden of breast cancer in Tanzania compared to the USA and Western Europe: male breast cancer and IBC.
doi:10.3233/BD-2009-0296
PMCID: PMC4276128  PMID: 21109721
Breast cancer; epidemiology; Tanzania; Sub-Saharan Africa; male breast cancer; inflammatory breast cancer
6.  Risk factors for VIA positivity and determinants of screening attendances in Dar es Salaam, Tanzania 
BMC Public Health  2012;12:1055.
Background
Tanzania is among the countries in the world where the cervical cancer incidence is estimated to be highest. Acknowledging an increase in the burden of cervical cancer, VIA was implemented as a regional cervical cancer screening strategy in Tanzania in 2002. With the aim of describing risk factors for VIA positivity and determinants of screening attendances in Tanzania, this paper present the results from a comparative analysis performed among women who are reached and not reached by the screening program”.
Methods
14 107 women aged 25–59 enrolled in a cervical cancer screening program in Dar es Salaam in the period 2002 – 2008. The women underwent VIA examination and took part in a structured questionnaire interview. Socioeconomic characteristics, sexual behavior, HIV status and high-risk (HR) HPV infection were determined in a subpopulation of 890 who participated and 845 who did not participate in the screening.
Results
Being widowed/separated OR=1.41 (95% CI: 1.17-1.66), of high parity OR=3.19 (95% CI: 1.84-5.48) of low education OR= 4.30 (95% CI: 3.50-5.31) and married at a young age OR=2.17 (95% CI: 1.37-3.07) were associated with being VIA positive. Women who participated in the screening were more likely to be HIV positive OR= 1.59 (95% CI. 1.14-2.25) in comparison with women who had never attended screening, while no difference was found in the prevalence of HR-HPV infection among women who had attended screening and women who had not attended screening.
Conclusion
Women who are widowed/separated, of high parity, of low education and married at a young age are more likely to be VIA positive and thus at risk of developing cervical cancer. The study further documents that a referral linkage between the HIV care and treatment program and the cervical cancer screening program is in place in the setting studied, where HIV positive were more likely to participate in the cervical cancer screening program than HIV negative women.
doi:10.1186/1471-2458-12-1055
PMCID: PMC3552680  PMID: 23216752
Cervical cancer; Screening; VIA; HPV; HIV; Tanzania
7.  A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt 
PLoS Medicine  2010;7(5):e1000270.
Analysis of a telephone survey by Gina Ogilvie and colleagues identifies the parental factors associated with HPV vaccine uptake in a school-based program in Canada.
Background
Information on factors that influence parental decisions for actual human papillomavirus (HPV) vaccine receipt in publicly funded, school-based HPV vaccine programs for girls is limited. We report on the level of uptake of the first dose of the HPV vaccine, and determine parental factors associated with receipt of the HPV vaccine, in a publicly funded school-based HPV vaccine program in British Columbia, Canada.
Methods and Findings
All parents of girls enrolled in grade 6 during the academic year of September 2008–June 2009 in the province of British Columbia were eligible to participate. Eligible households identified through the provincial public health information system were randomly selected and those who consented completed a validated survey exploring factors associated with HPV vaccine uptake. Bivariate and multivariate analyses were conducted to calculate adjusted odds ratios to identify the factors that were associated with parents' decision to vaccinate their daughter(s) against HPV. 2,025 parents agreed to complete the survey, and 65.1% (95% confidence interval [CI] 63.1–67.1) of parents in the survey reported that their daughters received the first dose of the HPV vaccine. In the same school-based vaccine program, 88.4% (95% CI 87.1–89.7) consented to the hepatitis B vaccine, and 86.5% (95% CI 85.1–87.9) consented to the meningococcal C vaccine. The main reasons for having a daughter receive the HPV vaccine were the effectiveness of the vaccine (47.9%), advice from a physician (8.7%), and concerns about daughter's health (8.4%). The main reasons for not having a daughter receive the HPV vaccine were concerns about HPV vaccine safety (29.2%), preference to wait until the daughter is older (15.6%), and not enough information to make an informed decision (12.6%). In multivariate analysis, overall attitudes to vaccines, the impact of the HPV vaccine on sexual practices, and childhood vaccine history were predictive of parents having a daughter receive the HPV vaccine in a publicly funded school-based HPV vaccine program. By contrast, having a family with two parents, having three or more children, and having more education was associated with a decreased likelihood of having a daughter receive the HPV vaccine.
Conclusions
This study is, to our knowledge, one of the first population-based assessments of factors associated with HPV vaccine uptake in a publicly funded school-based program worldwide. Policy makers need to consider that even with the removal of financial and health care barriers, parents, who are key decision makers in the uptake of this vaccine, are still hesitant to have their daughters receive the HPV vaccine, and strategies to ensure optimal HPV vaccine uptake need to be employed.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 10% of cancers in women occur in the cervix, the structure that connects the womb to the vagina. Every year, globally, more than a quarter of a million women die because of cervical cancer, which only occurs after the cervix has been infected with a human papillomavirus (HPV) through sexual intercourse. There are many types of HPV, a virus that infects the skin and the mucosa (the moist membranes that line various parts of the body, including the cervix). Although most people become infected with HPV at some time in their life, most never know they are infected. However, some HPV types cause harmless warts on the skin or around the genital area and several—in particular, HPV 16 and HPV 18, so-called high-risk HPVs—can cause cervical cancer. HPV infections are usually cleared by the immune system, but about 10% of women infected with a high-risk HPV develop a long-term infection that puts them at risk of developing cervical cancer.
Why Was This Study Done?
Screening programs have greatly reduced cervical cancer deaths in developed countries in recent decades by detecting the cancer early when it can be treated; but it would be better to prevent cervical cancer ever developing. Because HPV is necessary for the development of cervical cancer, vaccination of girls against HPV infection before the onset of sexual activity might be one way to do this. Scientists recently developed a vaccine that prevents infection with HPV 16 and HPV 18 (and with two HPVs that cause genital warts) and that should, therefore, reduce the incidence of cervical cancer. Publicly funded HPV vaccination programs are now planned or underway in several countries; but before girls can receive the HPV vaccine, parental consent is usually needed, so it is important to know what influences parental decisions about HPV vaccination. In this study, the researchers undertake a telephone survey to determine the uptake of the HPV vaccine by 11-year-old girls (grade 6) in British Columbia, Canada, and to determine the parental factors associated with vaccine uptake; British Columbia started a voluntary school-based HPV vaccine program in September 2008.
What Did the Researchers Do and Find?
In early 2009, the researchers contacted randomly selected parents of girls enrolled in grade 6 during the 2008–2009 academic year and asked them to complete a telephone survey that explored factors associated with HPV vaccine uptake. 65.1% of the 2,025 parents who completed the survey had consented to their daughter receiving the first dose of HPV vaccine. By contrast, more than 85% of the parents had consented to hepatitis B and meningitis C vaccination of their daughters. Nearly half of the parents surveyed said their main reason for consenting to HPV vaccination was the effectiveness of the vaccine. Conversely, nearly a third of the parents said concern about the vaccine's safety was their main reason for not consenting to vaccination and one in eight said they had been given insufficient information to make an informed decision. In a statistical analysis of the survey data, the researchers found that a positive parental attitude towards vaccination, a parental belief that HPV vaccination had limited impact on sexual practices, and completed childhood vaccination increased the likelihood of a daughter receiving the HPV vaccine. Having a family with two parents or three or more children and having well-educated parents decreased the likelihood of a daughter receiving the vaccine.
What Do These Findings Mean?
These findings provide one of the first population-based assessments of the factors that affect HPV vaccine uptake in a setting where there are no financial or health care barriers to vaccination. By identifying the factors associated with parental reluctance to agree to HPV vaccination for their daughters, these findings should help public-health officials design strategies to ensure optimal HPV vaccine uptake, although further studies are needed to discover why, for example, parents with more education are less likely to agree to vaccination than parents with less education. Importantly, the findings of this study, which are likely to be generalizable to other high-income countries, indicate that there is a continued need to ensure that the public receives credible, clear information about both the benefits and long-term safety of HPV vaccination.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000270.
The US National Cancer Institute provides information about cervical cancer for patients and for health professionals, including information on HPV vaccines (in English and Spanish)
The US Centers for Disease Control and Prevention also has information about cervical cancer and about HPV
The UK National Health Service Choices website has pages on cervical cancer and on HPV vaccination
More information about cervical cancer and HPV vaccination is available from the Macmillan cancer charity
ImmunizeBC provides general information about vaccination and information about HPV vaccination in British Columbia
MedlinePlus provides links to additional resources about cervical cancer (in English and Spanish)
doi:10.1371/journal.pmed.1000270
PMCID: PMC2864299  PMID: 20454567
8.  Long-Term Biological and Behavioural Impact of an Adolescent Sexual Health Intervention in Tanzania: Follow-up Survey of the Community-Based MEMA kwa Vijana Trial 
PLoS Medicine  2010;7(6):e1000287.
David Ross and colleagues conduct a follow-up survey of the community-based MEMA kwa Vijana (“Good things for young people”) trial in rural Tanzania to assess the long-term behavioral and biological impact of an adolescent sexual health intervention.
Background
The ability of specific behaviour-change interventions to reduce HIV infection in young people remains questionable. Since January 1999, an adolescent sexual and reproductive health (SRH) intervention has been implemented in ten randomly chosen intervention communities in rural Tanzania, within a community randomised trial (see below; NCT00248469). The intervention consisted of teacher-led, peer-assisted in-school education, youth-friendly health services, community activities, and youth condom promotion and distribution. Process evaluation in 1999–2002 showed high intervention quality and coverage. A 2001/2 intervention impact evaluation showed no impact on the primary outcomes of HIV seroincidence and herpes simplex virus type 2 (HSV-2) seroprevalence but found substantial improvements in SRH knowledge, reported attitudes, and some reported sexual behaviours. It was postulated that the impact on “upstream” knowledge, attitude, and reported behaviour outcomes seen at the 3-year follow-up would, in the longer term, lead to a reduction in HIV and HSV-2 infection rates and other biological outcomes. A further impact evaluation survey in 2007/8 (∼9 years post-intervention) tested this hypothesis.
Methods and Findings
This is a cross-sectional survey (June 2007 through July 2008) of 13,814 young people aged 15–30 y who had attended trial schools during the first phase of the MEMA kwa Vijana intervention trial (1999–2002). Prevalences of the primary outcomes HIV and HSV-2 were 1.8% and 25.9% in males and 4.0% and 41.4% in females, respectively. The intervention did not significantly reduce risk of HIV (males adjusted prevalence ratio [aPR] 0.91, 95%CI 0.50–1.65; females aPR 1.07, 95%CI 0.68–1.67) or HSV-2 (males aPR 0.94, 95%CI 0.77–1.15; females aPR 0.96, 95%CI 0.87–1.06). The intervention was associated with a reduction in the proportion of males reporting more than four sexual partners in their lifetime (aPR 0.87, 95%CI 0.78–0.97) and an increase in reported condom use at last sex with a non-regular partner among females (aPR 1.34, 95%CI 1.07–1.69). There was a clear and consistent beneficial impact on knowledge, but no significant impact on reported attitudes to sexual risk, reported pregnancies, or other reported sexual behaviours. The study population was likely to have been, on average, at lower risk of HIV and other sexually transmitted infections compared to other rural populations, as only youth who had reached year five of primary school were eligible.
Conclusions
SRH knowledge can be improved and retained long-term, but this intervention had only a limited effect on reported behaviour and no significant effect on HIV/STI prevalence. Youth interventions integrated within intensive, community-wide risk reduction programmes may be more successful and should be evaluated.
Trial Registration
ClinicalTrials.gov NCT00248469
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2.5 million people become infected with the human immunodeficiency virus (HIV), the virus that causes AIDS. HIV is most often spread through unprotected sex with an infected partner, so individuals can reduce their risk of HIV infection by abstaining from sex, by delaying first sex, by having few partners, and by always using a condom. And, because nearly half of new HIV infections occur among youths (15- to 24-year-olds), programs targeted at adolescents that encourage these protective behaviors could have a substantial impact on the HIV epidemic. One such program is the MEMA kwa Vijana (“Good things for young people”) program in rural Tanzania. This program includes in-school sexual and reproductive health (SRH) education for pupils in their last three years of primary education (12- to 15-year-olds) that provides them with the knowledge and skills needed to delay sexual debut and to reduce sexual risk taking. Between 1999 and 2002, the program was trialed in ten randomly chosen rural communities in the Mwanza Region of Tanzania; ten similar communities that did not receive the intervention acted as controls. Since 2004, the program has been scaled up to cover more communities.
Why Was This Study Done?
Although the quality and coverage of the MEMA kwa Vijana program was good, a 2001/2002 evaluation found no evidence that the intervention had reduced the incidence of HIV (the proportion of the young people in the trial who became HIV positive during the follow-up period) or the prevalence (the proportion of the young people in the trial who were HIV positive at the end of the follow-up period) of herpes simplex virus 2 (HSV-2, another sexually transmitted virus). However, the evaluation found improvements in SRH knowledge, in reported sexual attitudes, and in some reported sexual behaviors. Evaluations of other HIV prevention programs in other developing countries have also failed to provide strong evidence that such programs decrease the risk of HIV infection or other biological outcomes such as the frequency of other sexually transmitted infections or pregnancies, even when SRH knowledge improves. One possibility is that it takes some time for improved SRH knowledge to be reflected in true changes in sexual behavior and in HIV prevalence. In this follow-up study, therefore, researchers investigate the long-term impact of the MEMA kwa Vijana program on HIV and HSV-2 prevalence and ask whether the improvement in knowledge, reported attitudes and sexual risk behaviours seen at the 3-year follow up has persisted.
What Did the Researchers Do and Find?
In 2007/8, the researchers surveyed nearly 14,000 young people who had attended the trial schools between 1999 and 2002. Each participant had their HIV and HSV-2 status determined and answered questions (for example, “can HIV be caught by sexual intercourse (making love) with someone,” and “if a girl accepts a gift from a boy, must she agree to have sexual intercourse (make love) with him?”) to provide three composite sexual knowledge scores and one composite attitude score. 1.8% of the male and 4.0% of the female participants were HIV positive; 25.9% and 41.4% of the male and female participants, respectively, were HSV-2 positive. The prevalences were similar among the young people whose trial communities had been randomly allocated to receive the MEMA kwa Vijana Program and those whose communities had not received it, indicating that the MEMA kwa Vijana intervention program had not reduced the risk of HIV or HSV-2. The intervention program was associated, however, with a reduction in the proportion of men reporting more than four sexual partners in their lifetime and with an increase in reported condom use at last sex with a non-regular partner among women. Finally, although the intervention had still increased SRH knowledge, it now had had no impact on reported attitudes to sexual risk, reported pregnancies, or other reported risky sexual behaviors beyond what might have happened due to chance.
What Do These Findings Mean?
These findings indicate that, in the MEMA kwa Vijana trial, SRH knowledge improved and that this improved knowledge was retained for many years. Disappointingly, however, this intervention program had only a limited effect on reported sexual behaviors and no effect on HIV and HSV-2 prevalence at the 9-year follow-up. Although these findings may not be generalizable to other adolescent populations, they suggest that intervention programs that target only adolescents might not be particularly effective. Young people might find it hard to put their improved skills and knowledge into action when challenged, for example, by widespread community attitudes such as acceptance of older male–younger female relationships. Thus, the researchers suggest that the integration of youth HIV prevention programs within risk reduction programs that tackle sexual norms and expectations in all age groups might be a more successful approach and should be evaluated.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000287.
This study is further discussed in a PLoS Medicine Perspective by Rachel Jewkes
More information about the MEMA kwa Vijana program is available at their Web site
Information is available from the Programme for Research and Capacity Building in Sexual and Reproductive Health and HIV in Developing Countries on recent and ongoing research on HIV infection and other STIs
Information is available from the World Health Organization on HIV and on the health of young people
Information on HIV is available from UNAIDS
Information on HIV in children and adolescents is available from UNICEF
Information on HIV prevention interventions in the education sector is available from UNESCO
Information on HIV infection and AIDS is available from the US National Institute of Allergy and Infectious Diseases
The US Centers for Disease Control and Prevention provide information on HIV/AIDS and on HIV/AIDS among youth (in English and Spanish)
HIV InSitehas comprehensive information on all aspects of HIV/AIDS, including links to information on the prevention of HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS prevention and AIDS and sex education (in English and Spanish)
doi:10.1371/journal.pmed.1000287
PMCID: PMC2882431  PMID: 20543994
9.  Injectable and Oral Contraceptive Use and Cancers of the Breast, Cervix, Ovary, and Endometrium in Black South African Women: Case–Control Study 
PLoS Medicine  2012;9(3):e1001182.
A case-control study conducted in South Africa provides new estimates of the risk of specific cancers of the female reproductive system associated with use of injectable and oral contraceptives.
Background
Oral contraceptives are known to influence the risk of cancers of the female reproductive system. Evidence regarding the relationship between injectable contraceptives and these cancers is limited, especially in black South Africans, among whom injectable contraceptives are used more commonly than oral contraceptives.
Methods and Findings
We analysed data from a South African hospital-based case–control study of black females aged 18–79 y, comparing self-reported contraceptive use in patients with breast (n = 1,664), cervical (n = 2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported contraceptive use in 1,492 control patients diagnosed with cancers with no known relationship to hormonal contraceptive use. We adjusted for potential confounding factors, including age, calendar year of diagnosis, education, smoking, alcohol, parity/age at first birth, and number of sexual partners. Among controls, 26% had used injectable and 20% had used oral contraceptives. For current and more recent users versus never users of oral or injectable contraceptives, the odds ratios (ORs) for breast cancer were significantly increased in users of oral and/or injectable contraceptives (OR 1.66, 95% CI 1.28–2.16, p<0.001) and separately among those exclusively using oral (1.57, 1.03–2.40, p = 0.04) and exclusively using injectable (OR 1.83, 1.31–2.55, p<0.001) contraceptives; corresponding ORs for cervical cancer were 1.38 (1.08–1.77, p = 0.01), 1.01 (0.66–1.56, p = 0.96), and 1.58 (1.16–2.15, p = 0.004). There was no significant increase in breast or cervical cancer risk among women ceasing hormonal contraceptive use ≥10 y previously (p = 0.3 and p = 0.9, respectively). For durations of use ≥5 y versus never use, the ORs of ovarian cancer were 0.60 (0.36–0.99, p = 0.04) for oral and/or injectable contraceptive use and 0.07 (0.01–0.49, p = 0.008) for injectable use exclusively; corresponding ORs for endometrial cancer were 0.44 (0.22–0.86, p = 0.02) and 0.36 (0.11–1.26, p = 0.1).
Conclusions
In this study, use of oral and of injectable hormonal contraceptives was associated with a transiently increased risk of breast and cervical cancer and, for long durations of use, with a reduced risk of ovarian and endometrial cancer. The observed effects of injectable and of oral contraceptives on cancer risk in this study did not appear to differ substantially.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Hormonal contraceptives are among the most commonly used medications. Globally, more than 210 million women currently use either hormonal contraceptive pills or injectable contraceptives. Contraceptive pills usually contain manmade versions of the female sex hormones estrogen and progesterone (the combined oral contraceptive, or “pill”); most injectable hormonal contraceptives contain only manmade progesterone preparations. Hormonal contraceptives, which prevent pregnancy by disrupting the cyclical changes in estrogen and progesterone levels that prepare the body for pregnancy, have revolutionized birth control since they first became available in the early 1960s. However, it is now known that taking the pill also influences women's risk of developing cancers of the female reproductive system. Current and recent users have an increased risk of developing breast and cervical cancer (the cervix is the structure that connects the womb to the vagina) compared to never users, although this increased risk quickly disappears when women stop taking the pill. By contrast, women who have used the pill have a reduced risk of developing ovarian cancer and cancer of the womb (endometrial cancer) compared to never users that increases with the duration of pill use and persists for many years after use ceases. These effects on reproductive system cancers are thought to occur because these cancers depend on naturally occurring sex hormones for their development and growth.
Why Was This Study Done?
Although the evidence that the pill influences the risk of developing cancers of the female reproductive system is extensive, much less is known about how injectable hormonal contraceptives affect cancer risk. In this hospital-based case–control study (a study that compares the characteristics of people with and without a specific condition), the researchers investigate the relationship between the use of oral and injectable hormonal contraceptives and cancers of the breast, cervix, ovary, and endometrium among black South African women. Injectable contraceptives have been used for longer in South Africa than elsewhere and are used more commonly than oral contraceptives among black South African women.
What Did the Researchers Do and Find?
As part of the Johannesburg Cancer Case Control Study, which recruits black patients attending Johannesburg public referral hospitals for cancer treatment, the researchers compared hormonal contraceptive use in women with breast, cervical, ovarian, or endometrial cancer with contraceptive use in women diagnosed with other cancers such as lung, colon, and rectal cancers, which are not known to be influenced by hormonal contraceptives. Among the controls, a quarter had used injectable contraceptives and a fifth had used oral contraceptives. After adjusting for other factors that might influence cancer risk such as age, smoking, and number of sexual partners, the odds ratio (OR) of breast cancer among current and recent users of oral and/or injectable contraceptives compared to never users was 1.66. That is, the risk of developing breast cancer among current and recent users of hormonal contraceptives was 1.66 times that among never users. For women using oral contraceptives exclusively or injectable contraceptives exclusively, the ORs of breast cancer were 1.57 and 1.83, respectively. There were also increases in cervical cancer risk among current and recent users of hormonal contraceptives compared to never users, but no significant increase in breast or cervical cancer risk among women who had ceased hormonal contraceptive use more than ten years previously. Finally, the use of hormonal contraceptives for more than five years reduced the risk of both ovarian and endometrial cancer.
What Do These Findings Mean?
These findings indicate that, among black women in South Africa, the use of oral or injectable hormonal contraceptives is associated with a transiently increased risk of breast and cervical cancer, and that extended use of these contraceptives is associated with a reduced risk of ovarian and endometrial cancer. Moreover, they suggest that the effects of oral versus injectable contraceptives on cancer risk do not differ substantially, although for endometrial and ovarian cancer the small number of cases exposed to injectable contraceptives limits the accuracy of the risk estimates. Other limitations of this study include the possibility that the findings may be affected by uncontrolled confounding. That is, women who used hormonal contraceptives may have shared other unidentified characteristics that affected their cancer risk. Nevertheless, these findings provide new information about the effects of oral and injectable hormonal contraceptives on cancer risk that should help women make informed decisions about their choice of contraceptive method.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001182.
The US National Cancer Institute provides information on breast cancer (including personal stories from breast cancer survivors), cervical cancer, ovarian cancer, and endometrial cancer for patients and health professionals, and a fact sheet on oral contraceptives and cancer risk (in English and Spanish)
Cancer Research UK also provides information on breast cancer, cervical cancer, ovarian cancer, and endometrial cancer and information about the birth control pill and cancer risk
Eyes on the Prize, an online support group for women who have had cancers of the female reproductive system, has personal stories; further personal stories about breast, cervical, and ovarian cancer are provided by the charity Healthtalkonline
doi:10.1371/journal.pmed.1001182
PMCID: PMC3295825  PMID: 22412354
10.  Cervical cytological changes in HIV-infected patients attending care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania 
Background
Tanzania is among Sub-Saharan countries mostly affected by the HIV and AIDS pandemic, females being more vulnerable than males. HIV infected women appear to have a higher rate of persistent infection by high risk types of human papillomavirus (HPV) strongly associated with high-grade squamous intraepithelial lesions (HSIL) and invasive cervical carcinoma. Furthermore, although HIV infection and cervical cancer are major public health problems, the frequency and HIV/HPV association of cervical cancer and HSIL is not well documented in Tanzania, thus limiting the development of preventive and therapeutic strategies.
Methods
A prospective unmatched, case-control study of HIV-seropositive, ≥ 18 years of age and consenting non-pregnant patients attending the care and treatment center (CTC) at Muhimbili National Hoospital (MNH) as cases was done between 2005 and 2006. HIV seronegative, non-pregnant and consenting women recruited from the Cervical Cancer Screening unit (CCSU) at ORCI were used as controls while those who did not consent to study participation and/or individuals under < 18 years were excluded. Pap smears were collected for routine cytodiagnosis and P53 immunohistochemistry (IHC). Cervical lesions were classified according to the Modified Bethesda System.
Results
A total of 170 participants from the two centers were recruited including 50 HIV-seronegative controls were from the CCSU. Ages ranged from 20-66 years (mean 40.5 years) for cases and 20-69 years (mean 41.6 years) for controls. The age group 36-45 years was the most affected by HIV (39.2%, n = 47). Cervicitis, squamous intraepithelial lesions (SIL) and carcinoma constituted 28.3% (n = 34), 38.3% (n = 46) and 5.8% (n = 7) respectively among cases, and 28% (n = 14), 34% (n = 17) and 2% (n = 1) for controls, although this was not statistically significant (P-value = 0.61). IHC showed that p53 was not detectable in HPV + Pap smears and cell blocks indicating possible degradation.
Conclusions
The frequency of SIL and carcinoma appeared to be higher among HIV-infected women on HAART compared to seronegative controls and as expected increased with age. HIV seropositive patients appeared to present earlier with SIL compared to those HIV seronegative suggesting a role of HIV in altering the natural history of HPV infection and cervical lesions. The absence of p53 immunoreactivity in HPV + lesions is indicative of the ability of HPV E6 proteins to interact with the tumor suppressor gene and pave way for viral-induced oncogenesis in the studied Tanzanian women.
doi:10.1186/1750-9378-7-3
PMCID: PMC3298791  PMID: 22335893
11.  Brief Report: Knowledge, attitudes, practices and perceived risk of cervical cancer among Kenyan women 
OBJECTIVES
Eastern Africa has the highest incidence and mortality rates from cervical cancer worldwide. It is important to describe the differences among women and their perceived risk of cervical cancer in order to determine target groups to increase cervical cancer screening.
METHOD
In this cross-sectional study we surveyed women seeking reproductive health services in Kisumu, Kenya to assess their perceived risk of cervical cancer and risk factors influencing cervical cancer screening uptake. Chi-square statistics and t-tests were used to determine significant factors, which were incorporated into a logistic model to determine factors independently associated with cervical cancer risk perception.
RESULTS
While 91% of the surveyed women had heard of cancer, only 29% of the 388 surveyed women had previously heard of cervical cancer. The majority had received their information from healthcare workers. Few women (6%) had ever been screened for cervical cancer and cited barriers such as fear, time, and lacking knowledge about cervical cancer. Nearly all previously screened women (22/24, 92%) believed that cervical cancer was curable if detected early, and that screening should be conducted annually (86%). Most women (254/388, 65%) felt they were at risk for cervical cancer. Women with perceived risk of cervical cancer were older (OR=1.06, 95% CI 1.02, 1.10), reported a history of marriage (OR=2.08, CI 1.00, 4.30), were less likely to feel adequately informed about cervical cancer by healthcare providers (OR= 0.76, CI 0.18, 0.83) and more likely to intend to have cervical cancer screening in the future (OR= 10.59, CI 3.96, 28.30). Only 5% of women reported that they would not be willing to undergo screening, regardless of cost.
Conclusions
Cervical cancer is a major health burden for women in sub-Saharan Africa, yet only one-third of women had ever heard of cervical cancer in Kisumu, Kenya. Understanding factors associated with women’s perceived risk of cervical cancer could guide future educational and clinical interventions to increase cervical cancer screening.
doi:10.1097/IGC.0b013e31828e425c
PMCID: PMC3662490  PMID: 23694983
Screening; Barriers; Cervical Cancer; Africa
12.  Cervical cancer screening: knowledge, health perception and attendance rate among Hong Kong Chinese women 
Purpose:
Cervical cancer screening has been consistently shown to be effective in reducing the incidence rate and mortality from cervical cancer. However, cervical screening attendance rates are still far from satisfactory in many countries. Strategies, health promotion and education programs need to be developed with clear evidence of the causes and factors relating to the low attendance rate. The study aims to assess the prediction of cervical screening attendance rate by Chinese women’s knowledge about cervical cancer and cervical screening as well as their perception of health.
Patients and methods:
A survey with self-reported questionnaires was conducted on 385 Chinese women recruited from a community clinic in Hong Kong. Participants were Chinese women, Hong Kong residents, aged 18–65 years, able to read Chinese or English, and were not pregnant.
Results:
Women aged 37 years or less, with at least tertiary education, who perceived having control over their own health and had better knowledge on risk factors, were more likely to attend cervical cancer screening. Many participants had adequate general knowledge but were unable to identify correct answers on the risk factors.
Conclusion:
Health promotion efforts need to focus on increasing women’s knowledge on risk factors and enhancing their perceived health control by providing more information on the link between screening and early detection with lower incidence rates and mortality from cervical cancer.
PMCID: PMC2971734  PMID: 21072314
cervical screening attendance; cervical cancer; health perception and knowledge; perceived health control; Chinese
13.  Knowledge about Cervical Cancer and Barriers of Screening Program among Women in Wufeng County, a High-Incidence Region of Cervical Cancer in China 
PLoS ONE  2013;8(7):e67005.
Purpose
Cervical cancer screening is an effective method for reducing the incidence and mortality of cervical cancer, but the screening attendance rate in developing countries is far from satisfactory, especially in rural areas. Wufeng is a region of high cervical cancer incidence in China. This study aimed to investigate the issues that concern cervical cancer and screening and the factors that affect women’s willingness to undergo cervical cancer screening in the Wufeng area.
Participants and Methods
A cross-sectional survey of women was conducted to determine their knowledge about cervical cancer and screening, demographic characteristics and the barriers to screening.
Results
Women who were willing to undergo screenings had higher knowledge levels. “Anxious feeling once the disease was diagnosed” (47.6%), “No symptoms/discomfort” (34.1%) and “Do not know the benefits of cervical cancer screening” (13.4%) were the top three reasons for refusing cervical cancer screening. Women who were younger than 45 years old or who had lower incomes, positive family histories of cancer, secondary or higher levels of education, higher levels of knowledge and fewer barriers to screening were more willing to participate in cervical cancer screenings than women without these characteristics.
Conclusion
Efforts are needed to increase women’s knowledge about cervical cancer, especially the screening methods, and to improve their perceptions of the screening process for early detection to reduce cervical cancer incidence and mortality rates.
doi:10.1371/journal.pone.0067005
PMCID: PMC3699583  PMID: 23843976
14.  Anal Dysplasia Screening 
Executive Summary
Objective
This review considered the role of the anal Pap test as a screening test for anal dysplasia in patients at high risk of anal SCC. The screening process is now thought to be improved with the addition of testing for the human papillomavirus (HPV) in high-risk populations. High-resolution anoscopy (a method to view the rectal area, using an anoscope, a lighted instrument inserted into the rectum) rather than routine anoscopy-guided biopsy, is also now considered to be the diagnostic standard.
Clinical Need: Target Population and Condition
Anal cancer, like cervical cancer, is a member of a broader group of anogenital cancers known to be associated with sexually transmitted viral HPV infection. Human papillomavirus is extremely prevalent, particularly in young, sexually active populations. Sexual practices involving receptive anal intercourse lead to significantly elevated risk for anal dysplasia and cancer, particularly in those with immune dysfunctions.
Anal cancer is rare. It occurs at a rate of about 1 to 2 per 100,000 in the general population. It is the least common of the lower gastrointestinal cancers, representing about 4% of them, in contrast to colorectal cancers, which remain the third most commonly diagnosed malignancy. Certain segments of the population, however, such as HIV-positive men and women, other chronic immune-suppressed patients (e.g., after a transplant), injection drug users, and women with genital dysplasia /cancer, have a high susceptibility to anal cancer.
Those with the highest identified risk for anal cancer are HIV-positive homosexual and bisexual men, at a rate of 70 per 100,000 men. The risk for anal cancer is reported to be increasing dramatically in HIV-positive males and females, particularly since the introduction of highly active antiretroviral therapy in the mid-1990s. The introduction of effective viral therapy has been said to have transformed the AIDS epidemic in developed countries into a chronic disease state of long-term immunosuppression. In Ontario, there are about 25,000 people living with HIV infection; more than 6,000 of these are women. About 28% of the newly diagnosed HIV infections are in women, a doubling since 1999. It has also been estimated that 1 of 3 people living with HIV do no know it.
Health Technology Description
Anal Pap test screening involves the blind insertion of a swab into the anal canal and fixing cells either on a slide or in fluid for cytological examination. Anal cytology classified by the standardized Bethesda System is the same classification used for cervical cytology. It has 4 categories: normal, atypical squamous cells of uncertain significance, or squamous intraepithelial lesions which are further classified into low- or high-grade lesions. Abnormal cytological findings are subjected to further evaluations by high-resolution anoscopy, a technique similar to cervical colposcopy, and biopsy. Several HPV deoxyribonucleic acid detection technologies such as the Hybrid 11 Capture and the polymerase chain reaction are available to detect and differentiate HPV viral strains.
Unlike cervical cancer, there are no universally accepted guidelines or standards of care for anal dysplasia. Moreover, there are no formal screening programs provincially, nationally, or internationally. The New York State Department of Health AIDS Institute has recently recommended (March 2007) annual anal pap testing in high-risk groups. In Ontario, reimbursement exists only for Pap tests for cervical cancer screening. That is, there is no reimbursement for anal Pap testing in men or women, and HPV screening tests for cervical or anal cancer are also not reimbursed.
Methods
The scientific evidence base was evaluated through a systematic literature review. Assessments of current practices were obtained through consultations with various agencies and individuals including the Ministry of Health and Long-Term Care AIDS Bureau; Public Health Infectious Diseases Branch, Ministry of Health and Long-Term Care; Cancer Care Ontario; HIV/AIDS researchers; pathology experts; and HIV/AIDS clinical program directors. An Ontario-based budget impact was also done.
Findings
No direct evidence was found for the existence of controlled studies evaluating the effectiveness of anal Pap test screening programs for impact on anal cancer morbidity or mortality. In addition, no studies were found on the use of HPV DNA testing in the screening or diagnostic setting for anal dysplasia. The reported prevalence of HPV infection in high-risk groups, particularly HIV-positive males, however, was sufficiently high to preclude any utility of HPV testing as an adjunct to anal Pap testing.
Nine reports involving studies in the United States, United Kingdom, and Canada were identified that evaluated the performance characteristics of anal Pap test screening for anal dysplasia. All involved hospital-based specialty HIV/AIDS care clinics with mainly HIV-positive males. All studies involved experienced pathologists, so the results generally represent best-case scenarios. Estimates of anal Pap test sensitivity and specificity were highly variable, and depended on the varying prevalence of cytology abnormality and differential thresholds for abnormality for both cytology and histopathology.
In the largest study of HIV-positive males, sensitivity varied from 46% (95% confidence interval [CI], 36%–56%) to 69% (95% CI, 60%–78%). Specificity ranged from 59% (95% CI, 53%–65%) to 81% (95% CI, 76%–85%). In the only study of HIV-negative males, sensitivity ranged from 26% (95% CI, 5%-47%) to 47% (95% CI, 26%–68%). Specificity ranged from 81% (95% CI, 76%–85%) to 92% (95% CI, 89%–95%).
In comparison, cervical Pap testing has also been evaluated mainly in settings where there is a high prevalence of the disease, and estimates of sensitivitykij and specificity were also low and highly variable. In a systematic review involving cervical Pap testing, sensitivity ranged from 30% to 87% (mean, 47%) and specificity from 86% to 100% (mean, 95%).
Conclusions
No direct evidence exists to support the effectiveness of an anal Pap test screening program to reduce anal cancer mortality or morbidity. There are, however, strong parallels with cervical pap testing for cervical cancer. Sexually transmitted HPV viral infection is currently the acknowledged common causative agent for both anal and cervical cancer. Anal cancer rates in high-risk populations are approaching those of cervical cancer before the implementation of Pap testing.
The anal Pap test, although it has been mainly evaluated only in HIV-positive males, has similar operating characteristics of sensitivity and specificity as the cervical Pap test. In general, the treatment options for precancer dysplasia in the cervix and the anus are similar, but treatment involving a definitive surgical resection in the anus is more limited because of the higher risk of complications. A range of ablative therapies has been applied for anal dysplasia, but evidence on treatment effectiveness, tolerability and durability, particularly in the HIV-positive patient, is limited.
PMCID: PMC3377578  PMID: 23074504
15.  Determinants of Cervical screening services uptake among 18–49 year old women seeking services at the Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, Kenya 
Background
Kenyan women aged ≥15 years are at risk of developing cervical cancer. Currently, cervical cytology reduces cervical cancer incidence, since it allows for early diagnosis and treatment. Uptake of cervical screening services is a priority research area in Kenya. Central to the success of any screening programme is its ability to identify, reach out and screen the defined target population. Cervical screening coverage in Kenya is currently at 3.2%. In Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) in Nyanza, the number screened for cervical cancer is low (averagely 3/day). Thus the current study sought to identify factors influencing uptake of cervical screening services at the facility.
Methods
In a cross-sectional study, knowledge, perceptions and cues for action associated with self-reported cervical screening uptake were explored. The targeted population (n = 424), purposively selected were women of child-bearing age (18–49 years) visiting JOOTRH. Data on socio-demographic status (age, level of education, marital status, job status, income level), knowledge of cervical cancer, perceptions on severity and susceptibility to the disease were collected using self-administered structured questionnaires. Statistical significance of differences in proportions were determined by chi-square analyses while logistic regression analyses were used to identify determinants of self-reported uptake of the service.
Results
Self-reported screening uptake was 17.5%. There was a strong positive association between age (P < 0.0001), level of education (P < 0.0001) and income levels (P = 0.005) with the uptake of the service. Knowledge level on the signs and symptoms of cervical cancer was an important determinant for being screened for cervical cancer (P < 0.0001). Furthermore, those who said they didn’t know about the disease (OR, 26.84, 95% CI, 6.07-118.61, P < 0.0001) or were not aware about susceptibility to it (OR, 2.37, 95% CI, 1.10-5.08, P = 0.02) had a higher likelihood of not being screened. On cues for action, those who attended the child welfare clinic were more likely to be screened (OR, 2.31, 95% CI, 1.17-3.93, P = 0.03).
Conclusion
Knowledge, perception of higher susceptibility and attending child welfare clinic are key determinants of self-reported uptake of cervical screening. Increasing knowledge, enhancing health education and providing free services may increase uptake among women population in such settings.
Electronic supplementary material
The online version of this article (doi:10.1186/1472-6963-14-335) contains supplementary material, which is available to authorized users.
doi:10.1186/1472-6963-14-335
PMCID: PMC4271847  PMID: 25100298
Cervical; Women; Screening services; Determinants; Kenya
16.  Myths and misconceptions about cervical cancer among Zambian women: rapid assessment by peer educators 
Global health promotion  2010;17(2 0):47-50.
Objective
To make a rapid assessment of the common myths and misconceptions surrounding the causes of cervical cancer and lack of screening among unscreened low-income Zambian women.
Methods
We initiated a door-to-door community-based initiative, led by peer educators, to inform unscreened women about the existence of a new see-and-treat cervical cancer prevention program. During home visits peer educators posed the following two questions to women: 1. What do you think causes cervical cancer? 2. Why haven’t you been screened for cervical cancer? The most frequent types of responses gathered in this exercise were analyzed thematically.
Results
Peer educators contacted over 1100 unscreened women over a period of two months. Their median age was 33 years, a large majority (58%) were not educated beyond primary school, over two-thirds (71%) did not have monthly incomes over 500,000 Zambian Kwacha (US$100) per month, and just over half (51%) were married and cohabiting with their spouses. Approximately 75% of the women engaged in discussions had heard of cervical cancer and had heard of the new cervical cancer prevention program in the local clinic. The responses of unscreened low-income Zambian women to questions posed by peer educators in urban Lusaka reflect the variety of prevalent ‘folk’ myths and misconceptions surrounding cervical cancer and its prevention methods.
Conclusion
The information in our rapid assessment can serve as a basis for developing future educational and intervention campaigns for improving uptake of cervical cancer prevention services in Zambia. It also speaks to the necessity of ensuring that programs addressing women’s reproductive health take into account societal inputs at the time they are being developed and implemented. Taking a community-based participatory approach to program development and implementation will help ensure sustainability and impact.
doi:10.1177/1757975910363938
PMCID: PMC4123628  PMID: 20595342
cervical cancer; misconceptions; myths; peer educators
17.  Impact of health education intervention on knowledge and perception of cervical cancer and cervical screening uptake among adult women in rural communities in Nigeria 
BMC Public Health  2014;14(1):814.
Background
Cervical cancer is a disease of public health importance affecting many women and contributing to avoidably high levels of cancer deaths in Nigeria. In spite of the relative ease of prevention, the incidence is on the increase. This study aimed to determine the effect of health education on the awareness, knowledge and perception of cervical cancer and screening among women in rural Nigerian communities.
Methods
The study design was quasi-experimental. The study was carried out among adult women in Odogbolu (intervention) and Ikenne (control) local government areas (LGA) of Ogun state. Three hundred and fifty (350) women were selected per group by multistage random sampling technique. Data was collected by semi structured interviews with the aid of questionnaire. The intervention consisted of structured health education based on a movie.
Result
The intervention raised the level of awareness of cervical cancer and screening to 100% (p < 0.0001). The proportion of women with very good knowledge of cervical cancer and screening rose from 2% to 70.5% (χ2 = 503.7, p < 0.0001) while the proportion of those with good perception rose from 5.1% to 95.1% (p < 0.0001). The mean knowledge and mean perception scores were also increased (p < 0.0001). There was increase in the proportion of women who had undertaken cervical screening from 4.3% to 8.3% (p = 0.038). The major reason stated by the women for not having had cervical screening done was lack of awareness about cervical cancer and screening. There was statistically significant difference between the intervention and control groups concerning their knowledge attitude and practice towards cervical and screening (p < 0.05) after the intervention.
Conclusion
Multiple media health education based on a movie is effective in creating awareness for and improving the knowledge and perception of adult women about cervical cancer and screening. It also improves the uptake of cervical cancer screening. The creation of awareness is very crucial to the success of a cervical cancer prevention programme.
doi:10.1186/1471-2458-14-814
PMCID: PMC4133628  PMID: 25103189
Cervical cancer; Cervical screening; Knowledge; Perception; Awareness; Participatory health education; Movie
18.  Cervical cancer screening and adherence to follow-up among Hispanic women study protocol: a randomized controlled trial to increase the uptake of cervical cancer screening in Hispanic women 
BMC Cancer  2012;12:170.
Background
In the US, Hispanic women have a higher incidence of, and mortality from, cervical cancer than non-Hispanic white women. The reason for this disparity may be attributable to both low rates of screening and poor adherence to recommended diagnostic follow-up after an abnormal Pap test. The 'Cervical Cancer Screening and Adherence to Follow-up Among Hispanic Women' study is a collaboration between a research institution and community partners made up of members from community based organizations, the Yakima Valley Farm Workers Clinic and the Breast, Cervical, and Colon Health Program of the Yakima District . The study will assess the efficacy of two culturally-appropriate, tailored educational programs designed to increase cervical cancer screening among Hispanic women, based in the Yakima Valley, Washington, US.
Methods/design
A parallel randomized-controlled trial of 600 Hispanic women aged 21–64, who are non-compliant with Papanicolau (Pap) test screening guidelines. Participants will be randomized using block randomization to (1) a control arm (usual care); (2) a low-intensity information program, consisting of a Spanish-language video that educates women on the importance of cervical cancer screening; or (3) a high-intensity program consisting of the video plus a ‘promotora’ or lay-community health educator-led, home based intervention to encourage cervical cancer screening. Participants who attend cervical cancer screening, and receive a diagnosis of an abnormal Pap test will be assigned to a patient navigator who will provide support and information to promote adherence to follow-up tests, and any necessary surgery or treatment. Primary endpoint: Participants will be tracked via medical record review at community-based clinics, to identify women who have had a Pap test within 7 months of baseline assessment. Medical record reviewers will be blinded to randomization arm. Secondary endpoint: An evaluation of the patient navigator program as a method to improve adherence and reduce time to follow-up among participants who receive an abnormal Pap test result. An additional secondary endpoint is the cost-effectiveness of the two different intensity intervention programs.
Discussion
This culturally sensitive intervention aims to increase compliance and adherence to cervical screening in a Hispanic population. If effective, such interventions may reduce incidence of cervical cancer.
Trial registration
NCT01525433
doi:10.1186/1471-2407-12-170
PMCID: PMC3407514  PMID: 22559251
Hispanic women; Pap test; Cervical cancer screening; Cancer disparities
19.  Cancer Screening Practices Among Physicians in the National Breast and Cervical Cancer Early Detection Program 
Journal of Women's Health  2011;20(10):1479-1484.
Abstract
Background
The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides low-income, uninsured women with screening and diagnostic services for breast and cervical cancer. Our study was conducted to describe the demographic and practice characteristics of participating and nonparticipating physicians, as well as their beliefs, adoption of new screening technologies, and recommendations for breast and cervical cancer screening.
Methods
From a 2006–2007 nationally representative survey, we identified 1,111 practicing primary care physicians who provide breast and cervical cancer screenings and assessed their recommendations using clinical vignettes related to screening initiation, frequency, and cessation. Responses of physicians participating in the NBCCEDP were compared with those from nonparticipating physicians.
Results
Of the physicians surveyed, 15% reported participation in the NBCCEDP, 65% were not participants, and 20% were not sure or did not respond to this question. Program physicians were significantly more likely to practice in multispecialty settings, in a rural location, and in a hospital or clinic setting and had more patients who were female and insured by Medicaid or uninsured compared with nonprogram physicians. Beliefs about the effectiveness of screening tools or procedures in reducing breast or cervical cancer mortality were similar by program participation. Adoption of new technologies, including digital mammography and human papillomavirus (HPV) testing, and making guideline-consistent recommendations for screening initiation, frequency, and cessation did not differ significantly by program participation.
Conclusions
Although there may be differences in physician characteristics and practice settings, the beliefs and screening practices for both breast and cervical cancer are similar between program and nonprogram providers.
doi:10.1089/jwh.2010.2530
PMCID: PMC3233212  PMID: 21774673
20.  Awareness, perception and factors affecting utilization of cervical cancer screening services among women in Ibadan, Nigeria: a qualitative study 
Reproductive Health  2012;9:11.
Background
Over the years awareness and uptake of cervical cancer screening services has remained poor in developing countries. Problems associated with cervical cancer incidence include late reporting, ignorance and cultural issues relating to cervical cancer screening. This study sought to explore the awareness, perception and utilization of cervical cancer screening among women in Ibadan as well as factors that influence utilization.
Method
This is a qualitative study that utilized Eight Focus Group Discussions to collect information from women in selected health facilities in Ibadan, South West, Nigeria. The 82 participants were purposely recruited from women attending Antenatal clinics in 4 secondary and 4 primary health care facilities after approval was received from the Institutional Review Board in charge of the facilities. The focus group discussions were tape recorded and transcribed verbatim. The transcripts were analyzed into themes.
Findings
The study provided qualitative information on the awareness, perception of the utilization of cervical cancer screening services among women in Ibadan. Participants were mainly married women (92.7%), mean age =27.6, SD =4.5, mainly traders (39%) and from Yoruba ethnic backgrounds (87.8%) and had secondary education (39%). The respondents reported not being aware of cervical cancer and were not utilizing the services. Though they did not know what cervical cancer screening entailed or the screening methods, they still believed that it is important since like for other diseases will help in early detection and treatment. The participants were eager to get more information from nurses on cervical cancer about cervical cancer screening. The major factors identified by the women that influence screening utilization were ignorance, Illiteracy, belief in not being at risk, having many contending issues, nonchalant attitude to their health, financial constraint and fear of having a positive result.
Conclusion
There is an urgent need for more enlightenment about cervical cancer especially by health workers. Also, cervical cancer services should be made available at very affordable cost so that women can easily access the services in order to reduce incidence of invasive cancer.
doi:10.1186/1742-4755-9-11
PMCID: PMC3539913  PMID: 22866676
Awareness; Perception; Utilization; Cervical cancer screening; Women
21.  154 Responding to the challenge of AIDS Associated Cancers in Nigeria 
The stabilization of the HIV epidemic in Africa has uncovered new epidemic of HIV associated comorbidities including cancers which the poorly developed health care system, poor infrastructure and lack of personnel is unable to cope with. In November 2012, international leaders in Cancer Research and Policy from 15 countries met at the NIH, Bethesda and made recommendations about the interventions needed to respond to the global cancer challenge in the world. These include (1) Creation of reliable, population-based registries that define the incidence, mortality, and survival rates of different types of cancers (2) Implementation of prevention measures to mitigate factors now known to promote cancer—tobacco, certain infectious agents, ultraviolet radiation, alcohol, obesity, lack of exercise, and diet, (3) Screening individuals for certain cancers (of the cervix, breast, prostate, and colorectum, in particular) and (4) Optimal cancer treatment. In this presentation, I will highlight how the Institute of Human Virology, University of Maryland (IHV) and the Institute of Human Virology Nigeria (IHVN) working with partners in Nigeria and internationally have implemented these recommendations and present data illustrating the outcome of our interventions. For example,
Since 2010, 21 cancer registries have been developed or re-strengthened in Nigeria and 3 of these have met the WHO criteria for population based cancer registration (PBCR). These registries are now able to contribute data to the global cancer incidence database after more than 30 years during which there was no data from Nigeria. With mainstreaming of an additional 3 PBCR this year, we would have increased the proportion of Africa covered by PBCR from 11% to 32%. Our results also correct distortions in the estimates of cancer incidence and mortality in Nigeria which was previously based on projections derived from data from cancer registries of other African countries that had been used in the past.
Cervical cancer is the commonest female cancer in Africa and in women living with HIV/AIDS. Implementation of screening programs has reduced incidence in developed countries by 80% in recent decades but incidence in developing countries remain stable or has been increasing. IHV implements an innovative “screen and treat” with immediate treatment with cold coagulation, digital cervicography for QA/QC and web based consultation for second opinion for early detection of cervical cancer. In collaboration with the Nigerian authorities and other partners, this program plans to reach 1,000,000 Nigerian women with at least 1 lifetime screening event over the next 10 years.
This screening project laid the foundation for the NIH funded African Collaborative Center for Microbiome and Genomics Research (ACCME), part of the Wellcome Trust and NIH funded H3Africa initiative, which we set up at the IHVN and is currently engaged in integrative epidemiology of cervical cancer that is exploring the host and viral genomics and epigenomics, somatic cervical cancer genomics as part of NIH led Cancer Genome Atlas mapping project (TCGA), vaginal microenvironment—innate immunity and vaginal microbiota, as well as detailed risk factor characterization of prevalent and persistent HPV infection. Preliminary results from early studies conducted at this Center will be presented.
Because of dearth of systematic information about the epidemiology of AIDS Associated Cancers in Africa, we have created a matched prospective cohort of persons living with HIV/AIDS and healthy volunteers who are being followed up every 2 years with detailed clinical evaluation and collection of data and biological samples in order to improve knowledge of the epidemiology of HIV Associated Comorbidities and provide high quality biological samples for molecular and omics studies. In my presentation, I will also mention some of the trainings that we have conducted, research into other cancer risk factors and the work we are doing to map the infrastructural needs for oncology treatment in Nigeria.
doi:10.1097/01.qai.0000446738.38697.99
PMCID: PMC4149654
22.  Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies 
PLoS Medicine  2013;10(7):e1001492.
Ruth Pfeiffer and colleagues describe models to calculate absolute risks for breast, endometrial, and ovarian cancers for white, non-Hispanic women over 50 years old using easily obtainable risk factors.
Please see later in the article for the Editors' Summary
Background
Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer.
Methods and Findings
Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health–AARP Diet and Health Study [NIH-AARP]), we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT) use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI); the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort) the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96–1.04) for breast cancer and 1.08 (95% CI: 0.97–1.19) for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11–1.29). The areas under the receiver operating characteristic curves (AUCs; discriminatory power) were 0.58 (95% CI: 0.57–0.59), 0.59 (95% CI: 0.56–0.63), and 0.68 (95% CI: 0.66–0.70) for the breast, ovarian, and endometrial models, respectively.
Conclusions
These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may assist in clinical decision-making. Limitations are the modest discriminatory ability of the breast and ovarian models and that these models may not generalize to women of other races.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2008, just three types of cancer accounted for 10% of global cancer-related deaths. That year, about 460,000 women died from breast cancer (the most frequently diagnosed cancer among women and the fifth most common cause of cancer-related death). Another 140,000 women died from ovarian cancer, and 74,000 died from endometrial (womb) cancer (the 14th and 20th most common causes of cancer-related death, respectively). Although these three cancers originate in different tissues, they nevertheless share many risk factors. For example, current age, age at menarche (first period), and parity (the number of children a woman has had) are all strongly associated with breast, ovarian, and endometrial cancer risk. Because these cancers share many hormonal and epidemiological risk factors, a woman with a high breast cancer risk is also likely to have an above-average risk of developing ovarian or endometrial cancer.
Why Was This Study Done?
Several statistical models (for example, the Breast Cancer Risk Assessment Tool) have been developed that estimate a woman's absolute risk (probability) of developing breast cancer over the next few years or over her lifetime. Absolute risk prediction models are useful in the design of cancer prevention trials and can also help women make informed decisions about cancer prevention and treatment options. For example, a woman at high risk of breast cancer might decide to take tamoxifen for breast cancer prevention, but ideally she needs to know her absolute endometrial cancer risk before doing so because tamoxifen increases the risk of this cancer. Similarly, knowledge of her ovarian cancer risk might influence a woman's decision regarding prophylactic removal of her ovaries to reduce her breast cancer risk. There are few absolute risk prediction models for ovarian cancer, and none for endometrial cancer, so here the researchers develop models to predict the risk of these cancers and of breast cancer.
What Did the Researchers Do and Find?
Absolute risk prediction models are constructed by combining estimates for risk factors from cohorts with population-based incidence rates from cancer registries. Models are validated in an independent cohort by testing their ability to identify people with the disease in an independent cohort and their ability to predict the observed numbers of incident cases. The researchers used data on white, non-Hispanic women aged 50 years or older that were collected during two large prospective US cohort studies of cancer screening and of diet and health, and US cancer incidence and mortality rates provided by the Surveillance, Epidemiology, and End Results Program to build their models. The models all included parity as a risk factor, as well as other factors. The model for endometrial cancer, for example, also included menopausal status, age at menopause, body mass index (an indicator of the amount of body fat), oral contraceptive use, menopausal hormone therapy use, and an interaction term between menopausal hormone therapy use and body mass index. Individual women's risk for endometrial cancer calculated using this model ranged from 1.22% to 17.8% over the next 20 years depending on their exposure to various risk factors. Validation of the models using data from the US Nurses' Health Study indicated that the endometrial cancer model overestimated the risk of endometrial cancer but that the breast and ovarian cancer models were well calibrated—the predicted and observed risks for these cancers in the validation cohort agreed closely. Finally, the discriminatory power of the models (a measure of how well a model separates people who have a disease from people who do not have the disease) was modest for the breast and ovarian cancer models but somewhat better for the endometrial cancer model.
What Do These Findings Mean?
These findings show that breast, ovarian, and endometrial cancer can all be predicted using information on known risk factors for these cancers that is easily obtainable. Because these models were constructed and validated using data from white, non-Hispanic women aged 50 years or older, they may not accurately predict absolute risk for these cancers for women of other races or ethnicities. Moreover, the modest discriminatory power of the breast and ovarian cancer models means they cannot be used to decide which women should be routinely screened for these cancers. Importantly, however, these well-calibrated models should provide realistic information about an individual's risk of developing breast, ovarian, or endometrial cancer that can be used in clinical decision-making and that may assist in the identification of potential participants for research studies.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001492.
This study is further discussed in a PLOS Medicine Perspective by Lars Holmberg and Andrew Vickers
The US National Cancer Institute provides comprehensive information about cancer (in English and Spanish), including detailed information about breast cancer, ovarian cancer, and endometrial cancer;
Information on the Breast Cancer Risk Assessment Tool, the Surveillance, Epidemiology, and End Results Program, and on the prospective cohort study of screening and the diet and health study that provided the data used to build the models is also available on the NCI site
Cancer Research UK, a not-for-profit organization, provides information about cancer, including detailed information on breast cancer, ovarian cancer, and endometrial cancer
The UK National Health Service Choices website has information and personal stories about breast cancer, ovarian cancer, and endometrial cancer; the not-for-profit organization Healthtalkonline also provides personal stories about dealing with breast cancer and ovarian cancer
doi:10.1371/journal.pmed.1001492
PMCID: PMC3728034  PMID: 23935463
23.  The Preclinical Natural History of Serous Ovarian Cancer: Defining the Target for Early Detection 
PLoS Medicine  2009;6(7):e1000114.
Pat Brown and colleagues carry out a modeling study and define what properties a biomarker-based screening test would require in order to be clinically useful.
Background
Ovarian cancer kills approximately 15,000 women in the United States every year, and more than 140,000 women worldwide. Most deaths from ovarian cancer are caused by tumors of the serous histological type, which are rarely diagnosed before the cancer has spread. Rational design of a potentially life-saving early detection and intervention strategy requires understanding the lesions we must detect in order to prevent lethal progression. Little is known about the natural history of lethal serous ovarian cancers before they become clinically apparent. We can learn about this occult period by studying the unsuspected serous cancers that are discovered in a small fraction of apparently healthy women who undergo prophylactic bilateral salpingo-oophorectomy (PBSO).
Methods and Findings
We developed models for the growth, progression, and detection of occult serous cancers on the basis of a comprehensive analysis of published data on serous cancers discovered by PBSO in BRCA1 mutation carriers. Our analysis yielded several critical insights into the early natural history of serous ovarian cancer. First, these cancers spend on average more than 4 y as in situ, stage I, or stage II cancers and approximately 1 y as stage III or IV cancers before they become clinically apparent. Second, for most of the occult period, serous cancers are less than 1 cm in diameter, and not visible on gross examination of the ovaries and Fallopian tubes. Third, the median diameter of a serous ovarian cancer when it progresses to an advanced stage (stage III or IV) is about 3 cm. Fourth, to achieve 50% sensitivity in detecting tumors before they advance to stage III, an annual screen would need to detect tumors of 1.3 cm in diameter; 80% detection sensitivity would require detecting tumors less than 0.4 cm in diameter. Fifth, to achieve a 50% reduction in serous ovarian cancer mortality with an annual screen, a test would need to detect tumors of 0.5 cm in diameter.
Conclusions
Our analysis has formalized essential conditions for successful early detection of serous ovarian cancer. Although the window of opportunity for early detection of these cancers lasts for several years, developing a test sufficiently sensitive and specific to take advantage of that opportunity will be a challenge. We estimated that the tumors we would need to detect to achieve even 50% sensitivity are more than 200 times smaller than the clinically apparent serous cancers typically used to evaluate performance of candidate biomarkers; none of the biomarker assays reported to date comes close to the required level of performance. Overcoming the signal-to-noise problem inherent in detection of tiny tumors will likely require discovery of truly cancer-specific biomarkers or development of novel approaches beyond traditional blood protein biomarkers. While this study was limited to ovarian cancers of serous histological type and to those arising in BRCA1 mutation carriers specifically, we believe that the results are relevant to other hereditary serous cancers and to sporadic ovarian cancers. A similar approach could be applied to other cancers to aid in defining their early natural history and to guide rational design of an early detection strategy.
Please see later in the article for Editors' Summary
Editors' Summary
Background
Every year about 190,000 women develop ovarian cancer and more than 140,000 die from the disease. Ovarian cancer occurs when a cell on the surface of the ovaries (two small organs in the pelvis that produce eggs) or in the Fallopian tubes (which connect the ovaries to the womb) acquires genetic changes (mutations) that allow it to grow uncontrollably and to spread around the body (metastasize). For women whose cancer is diagnosed when it is confined to the site of origin—ovary or Fallopian tube—(stage I disease), the outlook is good; 70%–80% of these women survive for at least 5 y. However, very few ovarian cancers are diagnosed this early. Usually, by the time the cancer causes symptoms (often only vague abdominal pain and mild digestive disturbances), it has spread into the pelvis (stage II disease), into the space around the gut, stomach, and liver (stage III disease), or to distant organs (stage IV disease). Patients with advanced-stage ovarian cancer are treated with surgery and chemotherapy but, despite recent treatment improvements, only 15% of women diagnosed with stage IV disease survive for 5 y.
Why Was This Study Done?
Most deaths from ovarian cancer are caused by serous ovarian cancer, a tumor subtype that is rarely diagnosed before it has spread. Early detection of serous ovarian cancer would save the lives of many women but no one knows what these cancers look like before they spread or how long they grow before they become clinically apparent. Learning about this occult (hidden) period of ovarian cancer development by observing tumors from their birth to late-stage disease is not feasible. However, some aspects of the early natural history of ovarian cancer can be studied by using data collected from healthy women who have had their ovaries and Fallopian tubes removed (prophylactic bilateral salpingo-oophorectomy [PBSO]) because they have inherited a mutated version of the BRCA1 gene that increases their ovarian cancer risk. In a few of these women, unsuspected ovarian cancer is discovered during PBSO. In this study, the researchers identify and analyze the available reports on occult serous ovarian cancer found this way and then develop mathematical models describing the early natural history of ovarian cancer.
What Did the Researchers Do and Find?
The researchers first estimated the time period during which the detection of occult tumors might save lives using the data from these reports. Serous ovarian cancers, they estimated, spend more than 4 y as in situ (a very early stage of cancer development), stage I, or stage II cancers and about 1 y as stage III and IV cancers before they become clinically apparent. Next, the researchers used the data to develop mathematical models for the growth, progression, and diagnosis of serous ovarian cancer (the accuracy of which depends on the assumptions used to build the models and on the quality of the data fed into them). These models indicated that, for most of the occult period, serous cancers had a diameter of less than 1 cm (too small to be detected during surgery or by gross examination of the ovaries or Fallopian tubes) and that more than half of serous cancers had advanced to stage III/IV by the time they measured 3 cm across. Furthermore, to enable the detection of half of serous ovarian cancers before they reached stage III, an annual screening test would need to detect cancers with a diameter of 1.3 cm and to halve deaths from serous ovarian cancer, an annual screening test would need to detect 0.5-cm diameter tumors.
What Do These Findings Mean?
These findings suggest that the time period over which the early detection of serous ovarian cancer would save lives is surprisingly long. More soberingly, the authors find that a test that is sensitive and specific enough to take advantage of this “window of opportunity” would need to detect tumors hundreds of times smaller than clinically apparent serous cancers. So far no ovarian cancer-specific protein or other biomarker has been identified that could be used to develop a test that comes anywhere near this level of performance. Identification of truly ovarian cancer-specific biomarkers or novel strategies will be needed in order to take advantage of the window of opportunity. The stages prior to clinical presentation of other lethal cancers are still very poorly understood. Similar studies of the early natural history of these cancers could help guide the development of rational early detection strategies.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000114.
The US National Cancer Institute provides a brief description of what cancer is and how it develops and information on all aspects of ovarian cancer for patients and professionals. It also provides a fact sheet on BRCA1 mutations and cancer risk (in English and Spanish)
The UK charity Cancerbackup also provides information about all aspects of ovarian cancer
MedlinePlus provides a list of links to additional information about ovarian cancer (in English and Spanish)
The Canary Foundation is a nonprofit organization dedicated to development of effective strategies for early detection of cancers including ovarian cancer.
doi:10.1371/journal.pmed.1000114
PMCID: PMC2711307  PMID: 19636370
24.  Confusion regarding cervical cancer screening and chlamydia screening among sexually active young women 
Objective
The American Congress of Obstetricians and Gynecologists (ACOG) recently recommended that cervical cancer screening begin at 21 years of age and occur biennially for low-risk women younger than 30 years. Earlier studies suggested that women may have limited understanding of the differences between cervical cancer screening and chlamydia screening. This study assessed the knowledge of chlamydia and cervical cancer screening tests and schedules in younger women.
Methods
A survey regarding knowledge of chlamydia and cervical cancer screening was administered to 60 younger women aged 18–25 years in an obstetrics and gynaecology clinic at an urban community health centre.
Results
The majority of respondents recalled having had a Pap smear (93.3%) or chlamydia test (75.0%). Although many respondents understood that a Pap smear checks for cervical cancer (88.3%) and human papillomavirus (68.3%), 71.7% mistakenly believed that a Pap smear screens for chlamydia. No respondent correctly identified the revised cervical cancer screening schedule, and 83.3% selected annual screening. Few respondents (23.3%) identified the annual chlamydia screening schedule and 26.7% were unsure.
Conclusion
Many younger women in an urban community health centre believed that cervical cancer screening also screens for chlamydia and were confused about chlamydia screening schedules. As there is limited knowledge of the revised ACOG cervical cancer screening guidelines, there is a risk that currently low chlamydia screening rates may decrease further after these new guidelines are better known. Obstetrician gynaecologists and primary care providers should educate younger women about the differences between chlamydia and cervical cancer screening and encourage sexually active younger women to have annual chlamydia screening.
doi:10.1136/sextrans-2011-050289
PMCID: PMC3724364  PMID: 22123163
25.  Human papillomavirus (HPV) testing on self-collected specimens: perceptions among HIV positive women attending rural and urban clinics in South Africa 
Introduction
Cervical cancer is the most common cancer among women in Sub-Saharan Africa. Cervical cancer is treatable if detected timeously, yet only 20% of South African women have ever been for a Pap smear in their lifetime due to limited access to screening, transport or child care responsibilities.
Objective
To evaluate the acceptability of self-collection for cervical cancer screening. We aimed to identify which self-collection device women prefer and if they would consider using them for routine cervical cancer screening.
Methods
HIV-positive women (>18 years) from urban and rural HIV clinics were interviewed following an education session on HIV, human papillomavirus (HPV) and cervical cancer. Participants were shown three self-collection devices; (i) an Evalyn cervical brush, (ii) a Delphilavager and (iii) a tampon-like plastic wand before completing a short questionnaire.
Results
A total of 106 women from the urban (n = 52) and rural (n = 54) clinic were interviewed. Overall 51% of women preferred the cervical brush, while fewer women preferred the tampon-like plastic wand (31%) or lavage sampler (18%). More than 75% of women from the rural site preferred the cervical brush, compared to 22% from the urban site (p < 0.001). Women from the urban clinic preferred the tampon-like plastic wand (45%) and then the lavage sampler (33%), as compared to women from the rural clinic (19% and 4%, respectively).
Conclusion
Women from urban or rural settings had different preferences for the various self-collection devices. Patient self-collection with HPV testing may be an acceptable way to improve coverage to cervical cancer screening in high risk HIV-seropositive women.
doi:10.11604/pamj.2014.17.189.3454
PMCID: PMC4228994  PMID: 25396015
HIV-positive women; self-collection; human papillomavirus; acceptability; cervical cancer; resource-limited setting; South Africa

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