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1.  Human Papillomavirus Genotype Distributions: Implications for Vaccination and Cancer Screening in the United States 
Background
Limited data are available describing human papillomavirus (HPV) genotype distributions in cervical cancer in the United States. Such studies are needed to predict how HPV vaccination and HPV-based screening will influence cervical cancer prevention.
Methods
We used the New Mexico Surveillance, Epidemiology, and End Results Registry to ascertain cases of in situ (n = 1213) and invasive (n = 808) cervical cancer diagnosed during 1985–1999 and 1980–1999, respectively, in the state of New Mexico. HPV genotyping was performed using two polymerase chain reaction–based methods on paraffin-embedded tissues from in situ and invasive cancers and on cervical Papanicolaou test specimen from control subjects (ie, women aged 18–40 years attending clinics for routine cervical screening [n = 4007]). Relative risks for cervical cancer were estimated, and factors associated with age at cancer diagnosis and the prevalence of HPV genotypes in cancers were examined.
Results
The most common HPV genotypes detected in invasive cancers were HPV type 16 (HPV16, 53.2%), HPV18 (13.1%), and HPV45 (6.1%) and those in in situ cancers were HPV16 (56.3%), HPV31 (12.6%), and HPV33 (8.0%). Invasive cancer case subjects who were positive for HPV16 or 18 were diagnosed at younger ages than those who were positive for other carcinogenic HPV genotypes (mean age at diagnosis: 48.1 [95% confidence interval {CI} = 46.6 to 49.6 years], 45.9 [95% CI = 42.9 to 49.0 years], and 52.3 years [95% CI = 50.0 to 54.6 years], respectively). The proportion of HPV16-positive in situ and invasive cancers, but not of HPV18-positive cancers, declined with more recent calendar year of diagnosis, whereas the proportion positive for carcinogenic HPV genotypes other than HPV18 increased.
Conclusions
HPV16 and 18 caused the majority of invasive cervical cancer in this population sample of US women, but the proportion attributable to HPV16 declined over the last 20 years. The age at diagnosis of HPV16- and HPV18-related cancers was 5 years earlier than that of cancers caused by carcinogenic HPV genotypes other than HPV16 and 18, suggesting that the age at initiation of cervical screening could be delayed in HPV-vaccinated populations.
doi:10.1093/jnci/djn510
PMCID: PMC2664090  PMID: 19318628
2.  Human papillomavirus infections in women seeking cervical Papanicolaou cytology of Durango, Mexico: prevalence and genotypes 
Background
HPV infection in women from developing countries is an important public health problem. Therefore, we sought to determine the prevalences of HPV infection and HPV genotypes in a female population of Durango City, Mexico. Also to determine whether any socio-demographic characteristic from the women associated with HPV infection exists.
Methods
Four hundred and ninety eight women seeking cervical Papanicolaou examination in three public Health Centers were examined for HPV infection. All women were tested for HPV DNA PCR by using HPV universal primers. In addition, all positive HPV DNA PCR samples were further analyzed for genotyping of HPV genotype 16, 18 and 33. Socio-demographic characteristics from each participant were also obtained.
Results
Twenty-four out of four hundred and ninety-eight (4.8%) women were found infected by HPV. HPV genotype 16 was found in 18 out of the 24 (75%) infected women. Two of them were also coinfected by HPV genotype 18 (8.3%). In the rest 6 PCR positive women, genotyping for HPV genotypes 16, 18 and 33 were negative.
Conclusion
The prevalence of HPV in women of Durango City is low; however, most infected women have high risk HPV genotype. The women who were studied showed low frequency of risk factors for HPV infection and this may explain the low prevalence of HPV infection. The high frequency of high risk HPV genotypes observed might explain the high rate of mortality for cervical cancer in our region.
doi:10.1186/1471-2334-6-27
PMCID: PMC1388223  PMID: 16504014
3.  Prevalence and distribution of high-risk human papilloma virus (HPV) types in invasive squamous cell carcinoma of the cervix and in normal women in Andhra Pradesh, India 
Background
Despite the high incidence of cervical cancer reported from India, large scale population based studies on the HPV prevalence and genotype distribution are very few from this region. In view of the clinical trials for HPV vaccine taking place in India, it is of utmost importance to understand the prevalence of HPV genotypes in various geographical regions of India. We investigated the genotype distribution of high-risk HPV types in squamous cell carcinomas and the prevalence of high-risk HPV in cervicovaginal samples in the southern state of Andhra Pradesh (AP), India.
Methods
HPV genotyping was done in cervical cancer specimens (n = 41) obtained from women attending a regional cancer hospital in Hyderabad. HPV-DNA testing was also done in cervicovaginal samples (n = 185) collected from women enrolled in the cervical cancer screening pilot study conducted in the rural community, of Medchal Mandal, twenty kilometers away from Hyderabad.
Results
High-risk HPV types were found in 87.8% (n = 36/41) of the squamous cell carcinomas using a PCR-based line blot assay. Among the HPV positive cancers, the overall type distribution of the major high-risk HPV types was as follows: HPV 16 (66.7%), HPV 18 (19.4%), HPV 33 (5.6%), HPV 35 (5.6%), HPV 45 (5.6%), HPV 52 (2.8%), HPV 58(2.8%), HPV 59(2.8%) and HPV 73 (2.8%). Women participating in the community screening programme provided both a self-collected vaginal swab and a clinician-collected cervical swab for HPV DNA testing. Primary screening for high risk HPV was performed using the Digene Hybrid Capture 2 (hc2) assay. All hc2 positive samples by any one method of collection were further analyzed using the Roche PCR-based line blot for genotype determination. The prevalence of high risk HPV infection in this community-based screening population was 10.3% (19/185) using the clinician-collected and 7.0% (13/185) using the self-collected samples. The overall agreement between self-collected and clinician-collected samples was 92%; however among HPV-positive specimens, the HPV agreement was only moderate (39.1%). The most frequently detected HPV types in the Medchal community are HPV 52 and 16.
Conclusion
Our results suggest that the HPV type distribution in both cervical cancer tissues and in a general screening population from Andhra Pradesh is similar to that reported in India and other parts of the world. We also conclude that an effective vaccine targeting HPV 16 will reduce the cervical cancer burden in AP.
doi:10.1186/1471-2334-5-116
PMCID: PMC1345691  PMID: 16371167
4.  Human Papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain 
Background
Studies on HPV infection in pregnant women and HPV transmission to the child have yielded inconsistent results.
Methods
To estimate mother-to-child HPV transmission we carried out a prospective cohort study that included 66 HPV-positive and 77 HPV-negative pregnant women and their offspring attending a maternity hospital in Barcelona. To estimate HPV prevalence and genotype distribution in pregnancy we also carried out a related screening survey of cervical HPV-DNA detection among 828 pregnant women. Cervical cells from the mother were collected at pregnancy (mean of 31 weeks) and at the 6-week post-partum visit. Exfoliated cells from the mouth and external genitalia of the infants were collected around birth, at the 6-week post-partum visit, and around 3, 6, 12, and 24 months of age. All samples were tested for HPV using PCR. Associations between potential determinants of HPV infection in pregnant women and of HPV positivity in infants were also explored by logistic regression modelling.
Results
Overall cervical HPV-DNA detection in pregnant women recruited in the HPV screening survey was 6.5% (54/828). Sexual behavior-related variables, previous histories of genital warts or sexually transmitted infections, and presence of cytological abnormalities were statistically significantly and positively associated with HPV DNA detection in pregnant women recruited in the cohort. At 418 infant visits and a mean follow-up time of 14 months, 19.7% of infants born to HPV-positive mothers and 16.9% of those born to HPV-negative mothers tested HPV positive at some point during infants' follow-up. The most frequently detected genotype both in infants and mothers was HPV-16, after excluding untyped HPV infections. We found a strong and statistically significant association between mother's and child's HPV status at the 6-week post-partum visit. Thus, children of mothers' who were HPV-positive at the post-partum visit were about 5 times more likely to test HPV-positive than children of corresponding HPV-negative mothers (p = 0.02).
Conclusion
This study confirms that the risk of vertical transmission of HPV genotypes is relatively low. HPV persistence in infants is a rare event. These data also indicate that vertical transmission may not be the sole source of HPV infections in infants and provides partial evidence for horizontal mother-to-child HPV transmission.
doi:10.1186/1471-2334-9-74
PMCID: PMC2696457  PMID: 19473489
5.  Human Papillomavirus Infection in Women from Tlaxcala, Mexico 
Brazilian Journal of Microbiology  2010;41(3):749-756.
Cervical cancer is an important health problem in women living in developing countries. Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. Little information exists about HPV genotype distribution in rural and suburban regions of Mexico. Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one of the poorest states in central Mexico, and we evaluated age infection prevalence and risk factors associated with cervical neoplasm. A cross-sectional study was conducted in 236 women seeking gynecological care at the Mexican Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions (LGSIL, HGSIL). Parallel samples were used to detect HPV genotypes by PCR assays using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological questionnaire was applied. Prevalence of HPV infection was 31.3%. From the infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%; HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence (43.5%) was found in the 18- to 24-year-old group and the lowest (19%) in the 45- to 54-year-old group. None of the risk factors showed association with cervical neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present in 22% of normal samples and, of these, 82.6% represented high-risk HPVs. Tlaxcala showed HPV prevalence comparable to that of the largest cities in Mexico, with higher prevalence for HPV 31.
doi:10.1590/S1517-83822010000300027
PMCID: PMC3768634  PMID: 24031552
Epidemiology; Human papillomavirus; Mexico; PCR; Squamous intraepithelial lesions
6.  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
7.  A cross-sectional study to estimate high-risk human papillomavirus prevalence and type distribution in Italian women aged 18–26 years 
Background
Pre-vaccination information on HPV type-specific prevalence in target populations is essential for designing and monitoring immunization strategies for cervical cancer (CC) prevention. Data on HPV prevalence in Italy are available for women over the age of 24 years, target of the population-based CC screening programmes; while data of HPV prevalence in younger ages are very limited. The present study enrolled Italian women aged 18–26 years in order to assess the prevalence and distribution of high-risk (HR) HPV types. Risk-factors correlated with HR-HPV positivity were also described.
Methods
A sample of 2,289 women was randomly selected from the resident population lists of ten Local Health Units (LHUs) located in six Italian Regions scattered across the country; both rural and urban LHUs were involved. Women aged between 18 and 26 years and living in the selected LHUs were included in the study; pregnant women and women who did not speak Italian were excluded. A total of 1,102 women met the inclusion criteria and agreed to participate. Participants were offered pap test and Hybrid-Capture 2 (HC2) test for HR-HPV types and genotyping was performed on positive smears.
Results
Out of 1,094 valid samples, 205 (18.7%) were HR-HPV positive. Women with 2–4 (ORadj = 4.15, 95%CI: 2.56-6.72) and ≥5 lifetime partners (ORadj = 10.63, 95%CI: 6.16-18.36) and women who have used any contraceptive in the last six months (ORadj = 1.67, 95%CI: 1.09-2.54) had a higher risk to be infected; women living with their partner had a lower risk (ORadj = 0.56, 95%CI: 0.34-0.92) to acquire infection than women living with parents/friends/alone. Among HC2 positive women, HPV16 was the most prevalent type (30.9%), followed by 31 (19.6%), 66 (12.9%), 51 (11.3%), 18 (8.8%), 56 (8.8%). Co-infections of HR-HC2 targeted types were found in 20.4% of positive samples. The HR-HPV prevalence in women with abnormal cytology (52.4%) was significantly higher than in women with normal cytology (14.6%); however 33.0% of HR-HPV infected women had an abnormal cytology.
Conclusion
HR-HPV prevalence in Italian women aged 18–26 years was 19%, higher than what detected for older women, by other studies using the same molecular method and laboratory network; this result supports the choice of electing girls before the sexual debut as the primary target of HPV vaccination. The HPV type distribution found in this study may represent a baseline picture; an accurate post-vaccine surveillance is necessary to early detect a possible genotype replacement. The high prevalence of viral types other than vaccine-HPV types supports the necessity to guarantee the progression of CC screening programmes in vaccinated women.
doi:10.1186/1471-2334-13-74
PMCID: PMC3599585  PMID: 23390953
Human papillomavirus; High-risk types; Prevalence; Genotype distribution; Cervical cancer; Italy; Risk factors
8.  High prevalence of human papillomavirus infection in American Indian women of the Northern Plains 
Gynecologic oncology  2007;107(2):236-241.
Objectives
Cervical cancer is the leading gynecological malignancy worldwide, and the incidence of this disease is very high in American Indian women. Infection with the Human Papillomavirus (HPV) is responsible for more than 95% of cervical squamous carcinomas. Therefore, the main objective of this study was to analyze oncogenic HPV infections in American Indian women residing in the Northern Plains.
Methods
Cervical samples were collected from 287 women attending a Northern Plains American Indian reservation outpatient clinic. DNA was extracted from the cervical samples and HPV specific DNA were amplified by polymerase chain reaction (PCR) using the L1 consensus primer sets. The PCR products were hybridized with the Roche HPV Line Blot assay for HPV genotyping to detect 27 different low and high-risk HPV genotypes. The chi-square test was performed for statistical analysis of the HPV infection and cytology diagnosis data.
Results
Of the total 287 patients, 61 women (21.25%) tested positive for HPV infection. Among all HPV-positive women, 41 (67.2%) were infected with high-risk HPV types. Of the HPV infected women, 41% presented with multiple HPV genotypes. Additionally, of the women infected with oncogenic HPV types, 20 (48.7%) were infected with HPV 16 and 18 and the remaining 21 (51.3%) were infected with other oncogenic types (i.e., HPV59, 39, 73). Women infected with oncogenic HPV types had significantly higher (p=0.001) abnormal Papanicolaou smear tests (Pap test) compared to women who were either HPV negative or positive for non-oncogenic HPV types. The incidence of HPV infection was inversely correlated (p<0.05) with the age of the patients, but there was no correlation (p=0.33) with seasonal variation.
Conclusions
In this study, we observed a high prevalence of HPV infection in American Indian women residing on Northern Plains Reservations. In addition, a significant proportion of the oncogenic HPV infections were other than HPV16 and 18.
doi:10.1016/j.ygyno.2007.06.007
PMCID: PMC2396448  PMID: 17659767
Human Papillomavirus; American Indian; Northern Plains; Cervical cancer; Cervical cancer diagnosis
9.  Prevalence of human papillomavirus in young Italian women with normal cytology: how should we adapt the national vaccination policy? 
BMC Infectious Diseases  2013;13:575.
Background
Human Papillomavirus (HPV) is the most common sexually transmitted infection. In Italy, HPV vaccination is now offered free of charge to 12-year-old females. However, some regional health authorities have extended free vaccination to other age-groups, especially to girls under 18 years of age. We conducted a multicentre epidemiological study to ascertain the prevalence of different genotypes of HPV in young Italian women with normal cytology, with the aim of evaluating the possibility of extending vaccination to older females.
Methods
The study was performed in 2010. Women aged 16–26 years with normal cytology were studied. Cervical samples were analyzed to identify the presence of HPV by PCR amplification of a segment of ORF L1 (450 bp). All positive HPV-DNA samples underwent viral genotype analysis by means of a restriction fragment length polymorphism assay.
Results
Positivity for at least one HPV genotype was found in 18.2% of the 566 women recruited: 48.1% in the 16–17 age-class, 15.4 in the 18–20 age-class, 21.9% in the 21–23 age-class, and 15.5% in the 24–26 age-class; 10.1% of women were infected by at least one high-risk HPV genotype. HPV-16 was the most prevalent genotype. Only 4 (0.7%), 4 (0.7%) and 3 (0.5%) women were infected by HPV-18, HPV-6 and HPV-11, respectively. Of the HPV-DNA-positive women, 64.1% presented only one viral genotype, while 24.3% had multiple infections. The HPV genotypes most often involved in multiple infections were high-risk. A high prevalence was noted in the first years of sexual activity (48.1% of HPV-DNA-positive women aged 16–17 years); HPV prevalence subsequently declined and stabilized.
The estimate of cumulative proportions of young women free from any HPV infection at each age was evaluated; 93.3% and 97.1% of 26 year-old women proved free from HPV-16 and/or HPV-18 and from HPV-6 and/or HPV-11, respectively.
Conclusions
Our findings confirm the crucial importance of conducting studies on women without cytological damage, in order to optimise and up-date preventive interventions against HPV infection, and suggest that vaccinating 26-year-old females at the time of their first pap-test is to be recommend, though this issue should be further explored.
doi:10.1186/1471-2334-13-575
PMCID: PMC4029487  PMID: 24313984
Papillomavirus; HPV; Cervical cancer prevention; Vaccination; HPV epidemiology; Young women
10.  Human papillomavirus (HPV) prevalence and types among Turkish women at a gynecology outpatient unit 
Background
Human Papillomavirus (HPV) is a well-known pathogen for lower genital tract neoplasias, yet little is known regarding HPV prevalence in Turkey. The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among women with normal and abnormal cytology.
Methods
A total of five hundred seven (n = 507) women were retrospectively evaluated between 2004-2008. Conventional polymerase chain reaction was used to detect the presence of HPV types in cervicovaginal samples obtained from patients during gynecologic examination.
Results
One hundred four (n = 104) of the women were excluded from the study because of the incomplete data and a total of 403 women were used for the final analysis. There were, 93 (23%) women with cytologic abnormality and 310 (77%) women with normal cytology. Overall, 23% of the women was HPV positive. The overall prevalence of HPV in women with abnormal Pap smears was 36% (93/403), of which in ASCUS 22%, LSIL 51% and HSIL 60%. Also, HPV DNA was positive in 20% of the women with normal cervical cytology. The most common HPV types in cytologically normal women were as follows; HPV 16 (36%), HPV 6 (22%) and HPV 18 (13%). The rate of other HPV types were as follows; HPV11 4.4%, HPV45 4.4%, HPV90 4.4%, HPV35 2.2%, HPV67 2.2%, HPV81 2.2%, and multiple type HPVs 8.9%. The most common HPV types in cytologically abnormal women were HPV 16 (35%), HPV6 (19%) and HPV18 (8%). The rate of multiple HPV infections in women with normal Pap test was 2.2%.
Conclusion
HPV prevalence and type distribution in this study were similar to that reported worldwide at least in our study population. Hovewer, HPV prevalence was more common compared with previous studies reported from Turkey. This might be related with methodology and hospital based patient accrual and high rate of women with abnormal cytology. Further population based prospective studies are needed to eliminate the drawbacks of our study and to determine nonhospital based HPV prevalence in Turkish women.
doi:10.1186/1471-2334-9-191
PMCID: PMC2789077  PMID: 19948015
11.  Prevalence of cervical infection with HPV type 16 and 18 in Vietnam: implications for vaccine campaign 
BMC Cancer  2013;13:53.
Background
The Expanded Program on Immunization currently considers offering Human Papilomavirus vaccine on a routine basis in Vietnam. However, as the current available vaccine can prevent only two types HPV 16 and 18, before implementing a large-scale vaccine campaign we need information about the prevalence of infection with only HPV 16 and 18 in Viet Nam. This study was done in 5 large cities in Vietnam to estimate the prevalence of HPV 16 and/or 18 infections and to explore the distribution of other high risk types of HPV among married women in these provinces.
Methods
The study employed a cross-sectional design with multistage sampling. The sample size included 4500 married women in two rounds (aged ranged from 18-69 years old, median age: 40 year old). Participant were randomly selected, interviewed and given gynaecological examinations. HPV infection status (by real-time PCR kit using TaqMan probe) and HPV genotyping test (by Reverse dot blot) were done for all participants.
Results
The prevalence of cervical infection with HPV type 16 and/or 18 among married women in this study ranged from 3.1% to 7.4%. Many positive HPV cases (ranged from 24.5% to 56.8%) were infected with other type of high risk HPV which can lead to cervical cancer and cannot prevented by currently available vaccines. In addition to HPV 16 and/or 18, most common types of high risk HPV were types 58, 52, 35 and 45. Awareness about HPV and HPV vaccines was still low in the study samples.
Discussion
While it is relevant to implement an HPV vaccine campaign in Viet Nam, it is important to note that one can be infected with multiple types of HPV. Vaccination does not protected against all type of high risk HPV types. Future vaccine campaigns should openly disclose this information to women receiving vaccines.
Conclusion
High prevalence of infection with HPV high risk types was observed in this study. As HPV infection has a high correlation with cervical cancer, this study emphasizes the need for both primary prevention of cervical cancer with HPV vaccines as well as secondary prevention with screening.
doi:10.1186/1471-2407-13-53
PMCID: PMC3583820  PMID: 23374877
Cervical cancer; Human papilloma virus; Vietnam; HPV 16; HPV 18; HPV vaccine
12.  Multiple high risk HPV infections are common in cervical neoplasia and young women in a cervical screening population 
Journal of Clinical Pathology  2004;57(1):68-72.
Aims: If human papillomavirus (HPV) testing is to be included within cervical screening programmes, the importance of multiple HPV infections in cervical neoplasia needs to be determined. This study investigated the diversity of multiple HPV types in a routine cervical screening population, and assessed associations with cervical neoplasia.
Methods: Overall HPV prevalence, type specific prevalence, and extent of multiple infection were assessed in residual material from 3444 liquid based cytology samples, using real time GP5+/GP6+ polymerase chain reaction for screening and linear array assay for genotyping. HPV status was studied in relation to age and concurrent cytological evidence of dyskaryosis.
Results: Twenty per cent of samples were HPV positive. HPV type diversity was broad, and multiple HPV infections occurred in half of the HPV positive samples. Younger women were significantly more likely to harbour multiple high risk HPV (HR-HPV) infections. Infections with multiple HR-HPV types were found in 3.4% of samples negative for neoplasia and in 33.3%, 41.8%, and 40.4% of samples with borderline, mild, or high grade dyskaryosis, respectively. Single HR-HPV infections were found in 4.9%, 38.6%, 45.0%, and 51.1% of negative, borderline, mild, or high grade dyskaryosis samples, respectively.
Conclusions: Multiple HR-HPV infections were most prevalent in young women. Multiple HR-HPV infections were not more frequent in high grade than in low grade cervical neoplasia, reflecting common sexual transmission of multiple HR-HPV. Prospective cohort studies linking sequential loss or gain of HPV types with cytological analysis are required to assess the impact of multiple HR-HPV infections on neoplastic progression.
PMCID: PMC1770158  PMID: 14693839
human papillomavirus; multiple infection; cervical neoplasia
13.  The distribution of sexually-transmitted Human Papillomaviruses in HIV positive and negative patients in Zambia, Africa 
Background
Human Papillomaviruses (HPV) are double-stranded DNA viruses, considered to be the primary etiological agents in cervical intraepithelial neoplasias and cancers. Approximately 15–20 of the 40 mucosal HPVs confer a high-risk of progression of lesions to invasive cancer. In this study, we investigated the prevalence of sexually transmitted HPVs in Human Immunodeficiency Virus (HIV) positive and negative patients in Zambia, Africa. The rate of high-risk HPV genotypes worldwide varies within each country. Thus, we sought to investigate the rates of HPV infection in sub-Saharan Africa and the potential role of HIV in affecting the HPV genotype distribution.
Methods
This retrospective cross-sectional study reports findings on the association and effects of HIV on HPV infections in an existing cohort of patients at University Teaching Hospital (UTH) Lusaka, Zambia. The objective of this study was to assess HPV prevalence, genotype distribution and to identify co-factors that influence HPV infection. Polymerase chain reaction (PCR) with two standard consensus primer sets (CpI/II and GP5+/6+) was used to test for the presence of HPV DNA. Primers specific for β-actin were used to monitor DNA quality. Vaginal lavage samples, collected between 1998-1999 from a total of 70 women, were part of a larger cohort that was also analyzed for HIV and human herpesvirus infection. Seventy of the samples yielded usable DNA. HIV status was determined by two rapid assays, Capillus and Determine. The incidence of HIV and HPV infections and HPV genotype distributions were calculated and statistical significance was determined by Chi-Squared test.
Results
We determined that most common HPV genotypes detected among these Zambian patients were types 16 and 18 (21.6% each), which is approximately three-fold greater than the rates for HPV16, and ten-fold greater than the rates for HPV18 in the United States. The worldwide prevalence of HPV16 is approximately 14% and HPV18 is 5%. The overall ratio of high-risk (HR) to low-risk (LR) HPVs in the patient cohort was 69% and 31% respectively; essentially identical to that for the HR and LR distributions worldwide. However, we discovered that HIV positive patients were two-times as likely to have an HR HPV as HIV negative individuals, while the distribution of LR HPVs was unaffected by HIV status. Interestingly, we observed a nine-fold increase in HPV18 infection frequency in HIV positive versus HIV negative individuals.
Conclusion
The rate of oncogenic HPVs (type 16 and 18) in Zambia was much higher than in the U.S., potentially providing an explanation for the high-rates of cervical cancer in Zambia. Surprisingly, we discovered a strong association between positive HIV status and the prevalence of HR HPVs, and specifically HPV18.
doi:10.1186/1471-2334-7-77
PMCID: PMC1949816  PMID: 17634108
14.  Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer 
British Journal of Cancer  2011;105(5):694-697.
Background:
Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30–65 years, with the primary sample for HPV analysis taken by self-sampling.
Methods:
A total of 8000 women in Uppsala County, aged 30–65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test.
Results:
In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18–30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31–51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30–39 years to 24% in women at age 50–65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%).
Conclusion:
The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30–65 years.
doi:10.1038/bjc.2011.277
PMCID: PMC3188941  PMID: 21811250
cervix; screening; carcinoma; HPV test; persistence; self-sampling
15.  Significance of HPV-58 Infection in Women Who Are HPV-Positive, Cytology-Negative and Living in a Country with a High Prevalence of HPV-58 Infection 
PLoS ONE  2013;8(3):e58678.
Purpose
Cervical cytology and human papillomavirus (HPV) DNA co-testing is recommended as a screening method for detecting cervical lesions. However, for women who are HPV-positive but cytology-negative, the appropriate management and significance of HPV-58 infection remain unknown.
Methods
This study of prevalent HPV detected at baseline with a median follow-up of 3.2 years evaluated the risk factors associated with cervical abnormalities and assessed the significance of HPV-58 infection. A total of 265 women were enrolled. All high-grade squamous intraepithelial lesions (HSIL) that were detected by cytology were confirmed by histology. Histological diagnoses of cervical intraepithelial neoplasia 2/3 were classified as HSIL. Women were classified into four groups according to the HPV genotype that was detected at their first visit: HPV-58 (n = 27), HPV-16 (n = 52; 3 women had HPV-58 co-infection), ten other high risk (HR) types (n = 79), or low/undetermined risk types (n = 107).
Results
Of 265 women, 20 (7.5%) had HSIL on their follow-up examinations. There were significant differences in the cumulative incidence of HSIL between the four groups (p<0.001). The 5-year cumulative incidence rates of HSIL were 34.0% (95% CI: 17.3–59.8%) in HPV-58 positive cases, 28.0% (95% CI: 13.8–51.6) in HPV-16 positive cases, 5.5% (95% CI: 2.1–14.0%) in one of the ten other types of HR-HPV positive cases, and 0% in women with low/undetermined risk HPV. When seen in women with HR-HPV (n = 158), persistent HPV infection was a significant factor associated with the development of HSIL (hazard ratio = 15.459, 95% CI: 2.042–117.045). Women with HPV-58 had a higher risk (hazard ratio = 5.260, 95% CI: 1.538–17.987) for the development of HSIL than women with HPV-16 (hazard ratio = 3.822, 95% CI: 1.176–12.424) in comparison with women with other types of HR-HPV.
Conclusion
HPV-58 has a high association with the development of HSIL in women who are HPV-positive and cytology-negative.
doi:10.1371/journal.pone.0058678
PMCID: PMC3591398  PMID: 23505548
16.  Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study 
BMC Cancer  2009;9:275.
Background
Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy.
Methods
A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology.
Results
The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7) for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 – 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU.
Conclusion
Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.
doi:10.1186/1471-2407-9-275
PMCID: PMC2739859  PMID: 19664216
17.  HPV Type Distribution and Cervical Cytology among HIV-Positive Tanzanian and South African Women 
ISRN Obstetrics and Gynecology  2012;2012:514146.
Background. There are limited data on high-risk human papillomavirus (hr-HPV) genotypes among HIV-positive women in Africa, and little is known about their relationship with cervical cytology in these populations. Methods. We conducted a cross-sectional study among 194 HIV-positive women (143 from Tanzania, and 51 from South Africa) to evaluate HPV genotypes among HIV-positive women with normal and abnormal cytology. Cervical samples were genotyped for HPV types, and slides were evaluated for atypical squamous cell changes according to the Bethesda classification system. Results. Prevalence of high grade squamous intraepithelial dysplasia (HSIL) was 9%. Overall, more than half (56%) of women were infected with an hr-HPV type; 94% of women with HSIL (n = 16), 90% of women with LSIL (n = 35), and 42% of women within normal limits (WNL) (n = 58) tested positive for hr-HPV. Overall, the most prevalent hr-HPV subtypes were HPV16 (26%) and HPV52 (30%). Regional differences in the prevalence of HPV18 and HPV35 were found. Conclusion. Regional differences in HPV genotypes among African women warrant the need to consider different monitoring programmes for cervical preneoplasia. HPV-based screening tests for cervical preneoplasia would be highly inefficient unless coupled with cytology screening of the HPV-positive sample, especially in HIV-positive women.
doi:10.5402/2012/514146
PMCID: PMC3394385  PMID: 22811925
18.  Human Papillomavirus Prevalence and Genotype Distribution among HIV-Infected Women in Korea 
The epidemiology on human papillomavirus (HPV) among human immunodeficiency virus (HIV)-infected women in Korea is not well established. A retrospective study was conducted to determine the prevalence and genotype distribution of HPV infection among HIV-infected women in Korea. HPV DNA genotype and cervical cytology were examined in 60 HIV-positive women and 1,938 HIV-negative women. HPV genotypes were analyzed by using a HPV DNA chip. HIV-infected women had higher prevalence of high-risk HPV (hr-HPV) infection (30% vs 4.9%, adjusted odds ratio [AOR], 6.96; 95% confidence interval [CI], 3.63-13.34, P<0.001) and abnormal cervical cytology (18.3% vs 1.8%, AOR, 10.94; 95% CI, 5.18-23.1, P<0.001) compared with controls. The most common hr-HPV genotype detected in HIV-infected women was HPV 16 (10%), followed by 18 (6.7%) and 52 (5%). Prevalence of quadrivalent vaccine-preventable types (HPV 6, 11, 16, and 18) was 21.7% and 2.3% in HIV-positive women and HIV-negative women, respectively. Age was a significant risk factor for hr-HPV infection in HIV-infected women (P=0.039). The presence of hr-HPV was significantly associated with abnormal cervical cytology (P<0.001). These findings suggest that HPV testing for cervical cancer screening in HIV-infected women would be necessary, particularly among young age group.
doi:10.3346/jkms.2014.29.1.32
PMCID: PMC3890473  PMID: 24431902
HIV; Women; Human Papillomavirus; Prevalence; Genotype
19.  Human Papillomavirus 16, 18, 31 and 45 viral load, integration and methylation status stratified by cervical disease stage 
BMC Cancer  2014;14:384.
Background
Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45.
Methods
Samples singly infected with HPV16 (n = 226), HPV18 (n = 32), HPV31 (n = 75) or HPV45 (n = 29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3’L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample.
Results
Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2–26.1; p < 0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0–6.8; p = 0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8–18.0; p < 0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31.
Conclusions
This study lends support for HPV viral load and CpG methylation status, but not integration status, to be considered as potential biomarkers of cervical disease.
doi:10.1186/1471-2407-14-384
PMCID: PMC4053304  PMID: 24885011
Human papillomavirus; Cervical cancer; Genotypes; Viral load; Methylation; Integration
20.  Prevalence of HPV Infection and High Risk HPV Genotypes (16, 18), among Monogamous and Polygamous Women, In Zabol, Iran 
Iranian Journal of Public Health  2011;40(3):113-121.
Background:
This study was performed to compare the prevalence of HPV infection and high risk HPV genotypes [16, 18] between monogamous and polygamous women, in Zabol, Iran.
Methods:
This cross sectional study was conducted in Zabol in 2006 – 2007. Two hundred sixty five married women attending the Gynecology Clinic for Cervical Disease Screening entered to this study. One hundred sixty two cases had monogamous, and 103 had polygamous husbands. HPV PCR samples were obtained from scrape of papsmear specimens. The biotinylated primers MY09/MY11, GP5+/GP6+, were utilized to enable amplification and detection of positive PCR products. Confirmation of HPV-16 and -18 were done by type-specific PCR primers HPV-16/F, HPV-16/R and HPV-18/F, HPV-18/R.
Results:
Prevalence of HPV infection in monogamous and polygamous groups was 29% and 37.9%, respectively. The most HPV infection was found in 15–25 years group. The most prevalence of infection in monogamous group was HPV-18 and HPV-non16, 18 in 15–25 years, and HPV-16 in 26–35 years group. In polygamous group the most prevalent type was HPV-16, 18 in 15–25 years group. The most prevalent HPV-16 was seen in sever inflammation and dysplasia cytology in both groups.
Conclusion:
Prevalence of HPV infection in Zabol is high, and in women with polygamous husbands group is slightly more than monogamous. Screening for this infection must be recommended in this region of Iran.
PMCID: PMC3481649  PMID: 23113093
Human papillomavirus; Prevalence; High risk genotypes; Polygamy; Iran
21.  Type-specific prevalence of high-risk human papillomavirus by cervical cytology and age: Data from the health check-ups of 7,014 Korean women 
Obstetrics & Gynecology Science  2013;56(2):110-120.
Objective
We investigated the type-specific high-risk human papillomavirus (HPV) prevalence and distribution according to cervical cytology and age in healthy Korean women.
Methods
A retrospective cross-sectional study was conducted with 7,014 consecutive subjects undergoing both liquid-based cervical cytology and HPV genotyping test by DNA chip for cervical cancer screening. The type-specific prevalence and distribution of individual high-risk HPV types were assessed according to cervical cytology and age groups (<30, 30-39, 40-49, 50-59, and ≥60 years old).
Results
In total, the most common HPV genotype was HPV58 (23.9% of all high-risk HPV-positive subjects), followed by HPV16 (21.8%), HPV52 (16.6%), and HPV18 (11.7%). Regarding cervical cytology and age groups, the proportion of HPV56 strongly increased with the increasing severity of cervical cytology (P for trend=0.041). An age-specific decline in the overall high-risk HPV prevalence was reaffirmed, and the proportion of HPV52 declined markedly with age (P for trend=0.014).
Conclusion
The type-specific prevalence of high-risk HPV types significantly varies according to cervical cytology and age. It may imply that these types have different to develop into precancerous lesions in normal cervix.
doi:10.5468/OGS.2013.56.2.110
PMCID: PMC3784093  PMID: 24327989
Age; Cervical cytology; HPV; Prevalence
22.  HPV Genotype Distribution in Cervical Intraepithelial Neoplasia among HIV-Infected Women in Pune, India 
PLoS ONE  2012;7(6):e38731.
Background
The distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer.
Methods
HIV-infected women (N = 278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint.
Results
CIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and ‘carcinogenic’ HPV genotypes were present in 35.3% (98/278) HIV-infected women. ‘Possibly carcinogenic’ and ‘non/unknown carcinogenic’ HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (≥2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple ‘carcinogenic’ HPV genotypes were present in just over a quarter (27.8%) of women with ‘carcinogenic’ HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with ‘carcinogenic’ HPV type detection were reporting ≥2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy.
Conclusion
HPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies.
doi:10.1371/journal.pone.0038731
PMCID: PMC3378535  PMID: 22723879
23.  Prevalence of human papillomavirus in university young women 
Oncology Letters  2011;2(4):701-706.
Cervical cancer is the second most prevalent female cancer worldwide. The majority of cases appear between the age of 30 and 50. Human papillomavirus (HPV) plays a central role in cervical cancer with 99.7% of HPV DNA identified in invasive cervical carcinomas. The prevalence of the HPV infection varies substantially among countries and according to age and lifestyle. HPV is a common sexually transmitted infection among males and females with a 70% higher incidence in sexually active females. This study aimed to determine the prevalence of human papillomavirus in young university women by analyzing the correlation between Papanicolaou (PAP)-stained cervical tests and HPV detection by genotyping, as well as other risk factors. A total of 200 women aged between 18 and 25 years were enrolled in this study, which took place between September 2008 and May 2009 at the Universidad de Tarapacá, Arica, Chile. Results of the PAP smears showed that 97.5% of cells had normal characteristics, although an inflammatory pattern was noted. The prevalence of generic HPV infection was 3.5% when testing for HPV DNA using the polymerase chain reaction (PCR) method. An analysis of the genotype of infected female individuals indicated that high-risk HPV types, such as HPV 16 and 31 were present in 42.84 and 14.29% of females, respectively, and low-risk types such as HPV 6, in 14.29%. Only one sample with differentiated non-HPV (14.29%) was found. A 95% correlation between PAP-stained cervical tests and the method of testing for HPV was observed. Using the PCR method, it was found that of the 195 negative PAP smears, 5 were positive for HPV and two of the samples that were positive for ASC-US were also positive. A significantly increased (P<0.05) HPV infection risk was observed in the 18–21 age group with a higher prevalence (71.40%) when compared to the 22–25 age group (28.6%). A significant (P<0.042) difference was found between smoking and HPV infection. In conclusion, a significant (P<0.05) correlation was found between PAP and PCR methods for HPV testing in young university women. A significant correlation between smoking and HPV was detected, whereas no difference was noted with other parameters.
doi:10.3892/ol.2011.290
PMCID: PMC3406457  PMID: 22848252
human papillomavirus; prevalence
24.  Human Papillomavirus Type-Specific Prevalence in the Cervical Cancer Screening Population of Czech Women 
PLoS ONE  2013;8(11):e79156.
Background
Infection with high-risk human papillomavirus (HPV)types has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice.
Objectives
The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV.
Methods
Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2) and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB).
Results
Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393) of women were positive for any HPV type by BS-RLB, 18.2% (254/1393) by HR HC2, and 22.3% (310/1393) by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%). HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years.
Conclusions
Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future.
doi:10.1371/journal.pone.0079156
PMCID: PMC3827175  PMID: 24265750
25.  Next-generation sequencing of cervical DNA detects human papillomavirus types not detected by commercial kits 
Virology Journal  2012;9:164.
Background
Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV + women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women.
Methods
Total DNA was isolated from 109 cervical specimens from South African HIV + women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR.
Results
Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence’s of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6%, 12.8%, 4.6% and 8.3% respectively.
Conclusions
Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.
doi:10.1186/1743-422X-9-164
PMCID: PMC3493284  PMID: 22897914
Human papillomavirus; Human immunodeficiency virus; Next generation sequencing; Rolling circle amplification

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