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1.  Human Papillomavirus Infection in HIV-1 Infected Women in Catalonia (Spain): Implications for Prevention of Cervical Cancer 
PLoS ONE  2012;7(10):e47755.
Background
High-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women.
Methods
We enrolled 479 HIV-1–infected women from the PISCIS cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis.
Results
Median age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was 3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The factor associated with HR-HPV infection was age <30 years (odds ratio[OR],2.5; 95%confidence interval[CI],1.1–5.6). The factors associated with the presence of HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte count <200cells/mm3 versus >500cells/mm3 (OR,8.4; 95%CI,3.7–19.2), HIV-1 viral load >10,000copies/mL versus <400copies/mL (OR,2.1; 95%CI,1.0–4.4), and use of oral contraceptives (OR,2.0; 95%CI,1.0–3.9). Sixty percent of HIV-1–infected women had had one Pap smear within the last 2 years.
Conclusions
The high prevalence of HPV infection and cervical lesions in the HIV-1–infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and specific health education for HIV-1–infected women.
doi:10.1371/journal.pone.0047755
PMCID: PMC3484159  PMID: 23118894
2.  Detection of abnormal cervical cytology in Papanicolaou smears 
Background:
Cervical cytology by Papanicolaou (Pap) smears is an effective means of screening for cervical premalignant and malignant conditions. Cervical intra-epithelial neoplasia (CIN) and cervical cancer remain important health problems for women worldwide.
Aim:
To study the role of Pap smear in detecting premalignant and malignant lesions of cervix; and to determine the prevalence of various lesions.
Materials and Methods:
This study is based on 300 patients who attended the out-patient Department of Obstetrics and Gynaecology. Pap smears were prepared from patients presenting with complaints like vaginal discharge, post-coital bleeding, inter-menstrual bleeding, dyspareunia, and pain lower abdomen. After fixation and staining, each smear was carefully examined.
Results:
Epithelial cell abnormalities were found in 5% smears, atypical squamous cells of undetermined significance (ASCUS) in 0.3%, squamous intraepithelial lesion (SIL) in 3.4% which includes low grade squamous intraepithelial lesion (LSIL) (2.7%) and high grade squamous intraepithelial lesion (HSIL) 0.7%. Invasive carcinoma was seen in 1.3% cases. Mean age of the patients with diagnosis of LSIL was 32.3 years and for HSIL, it was 40.5 years. The mean age of the patients with invasive carcinoma was 57 years.
Conclusion:
Premalignant and malignant lesions of cervix are not uncommon in our set up and can be diagnosed early by Pap smears.
doi:10.4103/0970-9371.93222
PMCID: PMC3307451  PMID: 22438616
Cervical cancer; cervical intraepithelial neoplasia; papanicolaou smear
3.  Prevalence and risk factors for cervical squamous intraepithelial lesions among women infected with HIV-1 in Makurdi, Nigeria 
Background
The purpose of this study was to determine the prevalence and risk factors for cervical squamous intraepithelial lesions (SIL) among women infected with human immunodeficiency virus type 1 (HIV-1) receiving care at the Federal Medical Center Makurdi, Nigeria.
Methods
Between March and December 2009, a total of 253 women infected with HIV-1 had cervical smears taken for cytology. HIV-1 RNA viral load and CD4 counts were also measured.
Results
Of the 253 women, cervical SIL were present in 45 (17.8%). However, abnormal cervical cytology was noted in 146 (57.7%). Of those with abnormal cervical cytology, 101 (39.9%) women had atypical squamous cells of undetermined significance, 16 (6.3%) had low-grade SIL, and 29 (11.5%) women had high-grade SIL. The median CD4 lymphocyte count was lower in participants with cervical SIL compared with those without (132 versus 184 cells/mm3; P = 0.03). The median HIV-1 RNA viral load was higher in women with cervical SIL (102,705 versus 64,391 copies/mL; P = 0.02). A CD4 lymphocyte count of <200 cells/mm3 and an HIV-1 RNA viral load of <10,000 copies/mL were found to be significantly associated with cervical SIL.
Conclusion
A high prevalence of cervical SIL was found among HIV-1-infected women in Makurdi, Nigeria. Increased immune suppression and HIV-1 viremia are significantly associated with cervical SIL.
doi:10.2147/IJWH.S21205
PMCID: PMC3292404  PMID: 22393304
cervical squamous intraepithelial lesions; human immunodeficiency virus; risk factors; immunosuppression; cervical dysplasia; Nigeria
4.  Cervical Screening within HIV Care: Findings from an HIV-Positive Cohort in Ukraine 
PLoS ONE  2012;7(4):e34706.
Introduction
HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe.
Methods
Poisson regression models were fitted to data from 1120 women enrolled at three sites of the Ukraine Cohort Study of HIV-infected Childbearing Women to investigate factors associated with receiving cervical screening as part of HIV care. All women had been diagnosed as HIV-positive before or during their most recent pregnancy. Prevalence of cervical abnormalities (high/low grade squamous intraepithelial lesions) among women who had been screened was estimated, and associated factors explored.
Results
Overall, 30% (337/1120) of women had received a cervical screening test as part of HIV care at study enrolment (median 10 months postpartum), a third (115/334) of whom had been tested >12 months previously. In adjusted analyses, women diagnosed as HIV-positive during (vs before) their most recent pregnancy were significantly less likely to have a screening test reported, on adjusting for other potential risk factors (adjusted prevalence ratio (APR) 0.62, 95% CI 0.51–0.75 p<0.01 for 1st/2nd trimester diagnosis and APR 0.42, 95% CI 0.28–0.63 p<0.01 for 3rd trimester/intrapartum diagnosis). Among those with a cervical screening result reported at any time (including follow-up), 21% (68/325) had a finding of cervical abnormality. In adjusted analyses, Herpes simplex virus 2 seropositivity and a recent diagnosis of bacterial vaginosis were associated with an increased risk of abnormal cervical cytology (APR 1.83 95% CI 1.07–3.11 and APR 3.49 95% CI 2.11–5.76 respectively).
Conclusions
In this high risk population, cervical screening coverage as part of HIV care was low and could be improved by an organised cervical screening programme for HIV-positive women. Bacterial vaginosis testing and treatment may reduce vulnerability to cervical abnormalities.
doi:10.1371/journal.pone.0034706
PMCID: PMC3335834  PMID: 22545087
5.  Conventional Pap Smear Screening in HIV Seropositive Women in South India 
Objectives
To assess the prevalence of Pap smear abnormalities and to characterize the associated risk factors in HIV seropositive women.
Material and methods
We conducted a cross-sectional study on 252 HIV seropositive women in and around Krishna district, Andhra Pradesh, India by screening them for cervical cytological abnormalities by means of conventional Pap smear screening and the abnormalities reported as per modified Bethesda system.
Results
The prevalence of Pap smear abnormalities in HIV seropositive women was found to be 7.17 % which was a twofold increased risk as compared to the general population. On analysis of the risk factors like younger age for abnormal pap smears, mean CD4 count, duration of disease, and ART/HAART therapy the difference between the two groups of HIV seropositive women with normal pap smears and seropositive women with abnormal pap smears was found to be not statistically significant.
Conclusion
HIV/AIDS is associated with a twofold increased risk for cervical cytological abnormalities, and hence the need for periodic pap smear screening in this high risk group to reduce the global burden of cervical cancer.
doi:10.1007/s13224-012-0204-2
PMCID: PMC3650154  PMID: 24431601
HIV; Pap smear screening; Anti Retro Viral Therapy (ART); Highly Activated Anti Retro Viral Therapy (HAART); Cervical cytological abnormalities
6.  Human Papillomavirus Genotypes Associated With Cervical Cytologic Abnormalities and HIV Infection in Ugandan Women 
Journal of medical virology  2007;79(6):758-765.
Human papillomavirus (HPV) infection is associated with almost all cases of cervical cancer, and cervical cancer is a common malignancy in women living in developing countries. A cross-sectional study was conducted to determine the prevalence of HPV infection, human immunodeficiency virus (HIV) infection, and cervical cytologic abnormalities in women presenting to a sexually transmitted infections clinic in Kampala, Uganda. In June and July, 2002, 135 women underwent complete physical exams including Papanicolaou (Pap) smears. HIV status was evaluated by serology. Cervical and vaginal swabs were obtained by clinicians and tested for HPV genotypes by PCR/reverse blot strip assay. Of the 106 women with cervical swabs adequate for HPV testing, the HPV prevalence was 46.2% (49/106). HIV prevalence was 34.9% (37/106). High risk genotypes 52, 58, and 16 were the genotypes detected most commonly. Eighteen percent (9/49) of women infected with HPV were found to have genotypes 16 and/or 18. Seventy-three percent (27/37) of HIV-positive women versus 16% (10/63) of HIV-negative women had abnormal Pap smears (P <0.0001). Among HIV-positive women, abnormal Pap smears were associated with the presence of high risk HPV genotypes (P <0.001). The majority of women infected with HPV attending this sexually transmitted infections clinic in Uganda were infected with high risk HPV genotypes other than 16 and 18. Future studies should focus on whether current HPV vaccine formulations, that are limited to high risk genotypes 16 and 18, would be effective at decreasing the burden of cervical cancer in this population.
doi:10.1002/jmv.20817
PMCID: PMC2846524  PMID: 17457908
human papillomavirus (HPV); human immunodeficiency virus (HIV); HPV genotypes; cervical cytologic abnormalities; cervical cancer
7.  Predictors of persistent cytologic abnormalities after treatment of cervical intraepithelial neoplasia in Soweto, South Africa: a cohort study in a HIV high prevalence population 
BMC Cancer  2008;8:211.
Background
In the presence of both HIV infection and cervical intraepithelial neoplasia (CIN), the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ).
Methods
Women with high grade squamous intraepithelial lesions or worse (HSIL), less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap) smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regression
Results
The median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear.
Conclusion
We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer.
doi:10.1186/1471-2407-8-211
PMCID: PMC2515323  PMID: 18657270
8.  Self-reported history of Pap-smear in HIV-positive women in Northern Italy: a cross-sectional study 
BMC Cancer  2010;10:310.
Background
The incidence of invasive cervical cancer in HIV-positive women is higher than in the general population. There is evidence that HIV-positive women do not participate sufficiently in cervical cancer screening in Italy, where cervical cancer is more than 10-fold higher in women with AIDS than in the general population. The aim of the present study was to evaluate the history of Pap-smear in HIV-positive women in Italy in recent years. We also examined the sociodemographic, clinical, and organizational factors associated with adherence to cervical cancer screening.
Methods
A cross-sectional study was conducted between July 2006 and June 2007 in Emilia-Romagna region (Northern Italy). All HIV-positive women who received a follow-up visit in one of the 10 regional infectivology units were invited to participate. History of Pap-smear, including abnormal smears and subsequent treatment, was investigated through a self-administered anonymous questionnaire. The association between lack of Pap-smear in the year preceding the interview and selected characteristics was assessed by means of odds ratios (OR) and 95% confidence intervals adjusted for study centre and age.
Results
A total of 1,002 HIV-positive women were interviewed. Nine percent reported no history of Pap-smear, and 39% had no Pap-smear in the year prior to the date of questionnaire (last year). The lack of Pap-smear in the last year was significantly associated with age <35 years (OR = 1.4, compared to age ≥45 years), lower education level (OR = 1.3), first HIV-positive test in the last 2 years (OR = 1.4), and CD4 count <200 cells/μl (OR = 1.6). Conversely, when women were advised by a gynecologist rather than other health workers to undergo screening, it significantly increased adherence. Non-significantly higher proportions of lack of Pap-smear in the last year were found in women born in Central-Eastern Europe (OR = 1.8) and Africa (OR = 1.3). No difference in history of Pap-smear emerged by mode of HIV-acquisition or AIDS status.
Three hundred five (34%) women reported a previous abnormal Pap-smear, and of the 178 (58%) referred for treatment, 97% complied.
Conclusions
In recent years the self-reported history of Pap-smear in HIV-positive women, in some public clinics in Italy, is higher than previously reported, but further efforts are required to make sure cervical cancer screening is accessible to all HIV-positive women.
doi:10.1186/1471-2407-10-310
PMCID: PMC2904281  PMID: 20565935
9.  Human Papillomavirus Typing in HIV-Positive Women 
Objective: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), whichwere predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low- and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear.
Study design: HPV DNA typing (low- and high-risk) by Digene™ (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis.
Results: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears whichwere read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes.
Conclusion: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears.
doi:10.1155/S1064744901000163
PMCID: PMC1784640  PMID: 11495559
10.  Incidence of cervical disease associated to HPV in human immunodeficiency infected women under highly active antiretroviral therapy 
Background
Women infected with human immunodeficiency virus (HIV) may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV), HIV infection and Highly Active Antiretroviral Therapy (HAART) on the development of Squamous Intraepithelial lesions (SILs). Out of the 70 HIV infected women from Douala -Cameroon (Central Africa) that we included in the study, half (35) were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL).
Results
Assessment was done according to current antiretroviral regimens available nationwide and CD4 count. It was revealed that 44.3% of HIV-infected women had normal cytology. The overall prevalence of LSIL and HSIL associated to HPV in the studied groups was 24.3% (17/70) and 31.4% (22/70) respectively. Among the 22 HSIL-positive women, 63.6% (14/22) were not on antiretroviral therapy, while 36.4% (8/22) were under HAART. HIV infected women under HAART with positive HSIL, showed a median CD4+ T cell count of 253.7 +/- 31.7 higher than those without therapy (164.7 +/- 26.1). The incidence of HSIL related to HPV infection within the study group independently of HAART initiation was high.
Conclusion
These results suggest the need for extension and expansion of the current study in order to evaluate the incidence of HPV infection and cervical cancer among HIV-infected and non HIV- infected women in Cameroon.
doi:10.1186/1750-9378-4-9
PMCID: PMC2701409  PMID: 19493339
11.  The status of cervical cytology in Swaziland, Southern Africa: A descriptive study 
Cytojournal  2009;6:14.
Background:
Cancer of the cervix is the most common cancer in women in Swaziland where most women never undergo cervical screening. The extremely high prevalence of HIV/AIDS in Swaziland complicates the management of preinvasive and invasive cervical cancer. The purpose of this study was to assess the current status of cervical cytology in Swaziland, its strengths and limitations.
Methods:
The study is a retrospective review of 12,188 conventional cervical smears received by the Central Public Health Laboratory in Swaziland from June 2004 to May 2006.
Results:
Review of results showed very high rates of cytologic abnormalities with 43.2% of smears screened reported as abnormal. The percentages of abnormalities were as follows: atypical squamous cells of undermined significance (ASC-US), 19.8%; atypical squamous cells, cannot exclude HSILs (ASC-H), 8.8%; low-grade squamous intraepithelial lesions (LSIL), 9.0%; high-grade squamous intraepithelial lesions (HSIL), 4.6%; squamous cell carcinomas, 0.5%; atypical endocervical cells, 0.6%; and atypical endometrial cells, 0.4%. Just over 5% of smears were inadequate. The highest rates of HSILs and invasive squamous carcinoma occurred in women aged 50–59 years.
Conclusions:
This study underscores the need to reduce the incidence of cervical cancer and its precursor lesions in Swaziland women. Based on studies of human papillomavirus (HPV) types in other Southern African countries, current HPV vaccines would reduce the incidence and mortality from cervical cancer in the future, but cervical screening would still be required, both for women already infected with the HPV and for HPV subtypes not covered by current vaccines. The most cost-effective combination of screening modalities such as visual inspection, HPV DNA testing, and cytology should be investigated. Cervical cancer reduction needs to be managed within the greater framework of the HIV/AIDS epidemic.
doi:10.4103/1742-6413.54916
PMCID: PMC2758303  PMID: 19826481
Cervical screening; low resource communities; HPV
12.  Prevalence and predictors of squamous intraepithelial lesions of the cervix in HIV-infected women in Lusaka, Zambia 
Gynecologic oncology  2006;103(3):1017-1022.
Objectives
HIV-infected women living in resource-constrained nations like Zambia are now accessing antiretroviral therapy and thus may live long enough for HPV-induced cervical cancer to manifest and progress. We evaluated the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Zambia.
Methods
We screened 150 consecutive, non-pregnant HIV-infected women accessing HIV/AIDS care services in Lusaka, Zambia. We collected cervical specimens for cytological analysis by liquid-based monolayer cytology (ThinPrep Pap Test®) and HPV typing using the Roche Linear Array® PCR assay.
Results
The median age of study participants was 36 years (range 23-49 years) and their median CD4+ count was 165/μL (range 7-942). The prevalence of SIL on cytology was 76% (114/150), of which 23.3% (35/150) women had low-grade SIL, 32.6% (49/150) had high-grade SIL, and 20% (30/150) had lesions suspicious for squamous cell carcinoma (SCC). High-risk HPV types were present in 85.3% (128/150) women. On univariate analyses, age of the participant, CD4+ cell count, and presence of any high-risk HPV type were significantly associated with the presence of severely abnormal cytological lesions (i.e., high-grade SIL and lesions suspicious for SCC). Multivariable logistic regression modeling suggested the presence of any high-risk HPV type as an independent predictor of severely abnormal cytology (adjusted OR: 12.4, 95% CI 2.62-58.1, p=0.02).
Conclusions
The high prevalence of abnormal squamous cytology in our study is one of the highest reported in any population worldwide. Screening of HIV-infected women in resource-constrained settings like Zambia should be implemented to prevent development of HPV-induced SCC.
doi:10.1016/j.ygyno.2006.06.015
PMCID: PMC2748907  PMID: 16875716
HIV; Cervical Cancer; Screening; Cytology; Zambia
13.  Screening for Human Immunodeficiency Virus in Inner City Females With Abnormal Cervical Cytology 
Objective: This report evaluates the acceptance, results, and predictors of human immunodeficiency virus (HIV) infection in inner city women referred to a colposcopy clinic for abnormal cervical cytology.
Methods: HIV testing results of 1,908 inner city women referred for abnormal cervical cytology were analyzed retrospectively with respect to acceptance, race, ethnicity, Pap smear results, sexually transmitted diseases (STDs), HIV exposures, and final histologic findings.
Results: HIV testing was accepted by 50.4% of patients. Women who agreed to screening were significantly more likely to admit exposure to HIV or to be Hispanic, foreign-born, or have a history of multiple STDs. Of those screened, 3.3% were found to be HIV seropositive. Although higher grades of referral Pap smears were noted in the women found to be HIV seropositive, final histologic findings were not different. The only predictors of unknown HIV seropositivity were admitted HIV exposure and external condyloma.
Conclusions: Fifty percent of inner city women of unknown HIV status referred for abnormal cervical cytology will accept HIV serotesting and 3.3% are found to be positive. Most HIV-seropositive women can be detected based on either a history of exposure to HIV or the presence of external condyloma.
doi:10.1155/S1064744996000543
PMCID: PMC2364508  PMID: 18476108
14.  Association of Trichomonas vaginalis and Cytological Abnormalities of the Cervix in Low Risk Women 
PLoS ONE  2013;8(12):e86266.
Objective
Is Trichomonas vaginalis (TV) an inducing factor for the development of (pre-)cancerous lesions of the cervix?
Design
Cross sectional study.
Setting
Screening healthy Belgian women with low infection risk.
Sample
63,251 consecutive liquid based cervical samples.
Methods
Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities.
Main Outcome Measures
Association of TV and HPV with cervix dysplasia
Results
The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6). In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05), mainly due to an increase in ASC-US and LSIL, but not HSIL.
Conclusions
We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.
doi:10.1371/journal.pone.0086266
PMCID: PMC3875579  PMID: 24386492
15.  12-county program: screening of 34,318 women for cervical cancer in California, 1975-78. 
Public Health Reports  1981;96(6):547-554.
The California Department of Health Services conducted a cervical cancer screening program in 12 counties where local health agencies provided the screening services. A major purpose of the study was to screen women at high risk of cervical cancer and to assure that women with abnormal results on cervical cytology testing obtained appropriate diagnostic workup and treatment. A total of 34,318 women were screened, and 7,811 returned for up to 3 annual rescreening examinations. Final cytologic results were 33,658 normal, 100 unsatisfactory, and 560 abnormal smears. Of the abnormal smears, 484 were indicative of cervical dysplasia, 41 of in situ cervical cancer and 22 of invasive cervical cancer. In 13 women, endometrial cancer was suspected. Complete followup information on diagnostic evaluation and treatment was obtained for 80 percent of the women with abnormal Pap test results. Histological confirmation of neoplasia was reported for 173 women. The diagnoses were cervical dysplasia in 108, cervical cancer in 58 (49 in situ, 9 invasive) and endometrial cancer in 7. The program reached greater proportions of older women, the less affluent, women of Spanish origin and oriental women and a smaller proportion of blacks than were present in the general female population of California.
PMCID: PMC1424263  PMID: 7302109
16.  Comparison of Conventional Cervical Cytology versus Visual Inspection with Acetic Acid (VIA) among HIV-Infected Women in Western Kenya 
Objective
To determine the accuracy of visual inspection with Acetic Acid (VIA) versus conventional Pap smear as a screening tool for cervical intraepithelial neoplasia (CIN)/cancer among HIV-infected women.
Materials and Methods
150 HIV-infected women attending the Moi Teaching and Referral Hospital HIV clinic in Eldoret underwent conventional Pap smear, VIA, colposcopy and biopsy. VIA and Pap smears were done by nurses while colposcopy and biopsy were done by a physician. Receiver Operating Characteristic (ROC) analysis was conducted to compare the accuracies between VIA and Pap smear in sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Results
Among the study participants: VIA was abnormal in 55.3% (83/150, CI=47.0–63.5%); Pap smear showed atypical squamous cells of undetermined significance (ASCUS) or worse in 43.7% (59/135, CI=35.2–52.5%) and 10% (15/150) of the Pap smears were unsatisfactory. Of the abnormal Pap smears, 3% (2/59) had ASCUS, 7% (4/59) had ASC-high grade, 60% (35/59) had low-grade squamous intraepithelial lesions (SIL), 29% (17/59) had high grade SIL, and 2% (1/59) was suspicious for cervical cancer. Using cervical intraepithelial neoplasia (CIN) 2 or higher disease on biopsy as an end point, VIA has a sensitivity of 69.6% (CI=55.1–81.0%), specificity of 51.0% (CI=41.5–60.4%), PPV of 38.6% (CI=28.8–49.3%) and NPV of 79.1% (CI=67.8–87.2%). For conventional Pap smear, sensitivity was 52.5% (CI=42.1–71.5%), specificity 66.3% (CI=52.0–71.2%), PPV 39.7% (CI=27.6–51.8%), and NPV 76.8% (CI=67.0–85.6%).
Conclusion
VIA is comparable to Pap smear and acceptable for screening HIV-infected women in resource limited settings such as Western Kenya.
doi:10.1097/LGT.0b013e3182320f0c
PMCID: PMC3289722  PMID: 22126834
Visual Inspection with Acetic Acid (VIA); Pap smear; Kenya; HIV
17.  Prevalence of cervical dysplasia in western Uttar Pradesh 
Introduction:
Cervical intraepithelial neoplasia and cervical cancer remain important health problems. Cervical cytology by Papanicolaou (Pap) smears is an effective means of screening for cervical premalignant and malignant conditions.
Aim:
The aim of this study was to assess the prevalence of cervical dysplasia in pre- and postmenopausal women in western Uttar Pradesh and to find out risk factors as far as possible.
Materials and Methods:
A total of 4,703 cases were enrolled, cervical scrape smears were collected and stained using Papanicolaou's method and hematoxylin and eosin stain. The emphasis was put on epithelial abnormalities and smears were classified according to The Bethesda System 2001.
Results:
81.06% (3812) smears were satisfactory according to The Bethesda System. Maximum numbers of cases (40.37%) were in age group 30-39 years. The epithelial abnormalities constituted 3.23% of all cases. Low-grade squamous intraepithelial lesion (LSIL) formed the largest number (1.36%), while high-grade squamous intraepithelial lesion (HSIL) formed 0.91%. Eleven cases of squamous cell carcinoma (SCC) were detected. The study has shown a relatively high prevalence of epithelial abnormalities in cervical smears with increasing age, parity, early age at first coitus (<20 year), and lower socioeconomic status in symptomatic women with clinical lesions on per speculum examination.
Conclusion:
Epithelial abnormalities of cervix are not uncommon in our setup and are associated with early age at marriage and parity.
doi:10.4103/0970-9371.126659
PMCID: PMC3945627  PMID: 24648670
Carcinoma cervix; cervical intraepithelial neoplasia; HSIL; LSIL; papanicolaou smear
18.  Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study 
BMJ : British Medical Journal  2002;325(7364):572.
Objectives
To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types.
Design
Population based prospective cohort study.
Setting
General population in Copenhagen, Denmark.
Participants
10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions).
Main outcome measures
Results of cervical smear tests and cervical swabs at enrolment and at the second examination about two years later.
Results
Compared with women who were negative for human papillomavirus at enrolment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2).
Conclusions
Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.
What is already known on this topicPersistence of infection with human papillomavirus (HPV) is thought to have a role in the development of cervical neoplasiaPrevious studies have included only a few cases of high grade squamous intraepithelial lesions, and few have randomly sampled women from the general populationWhat this study addsIn women aged 20-29, HPV infection preceded the development of high grade lesionsPersistent HPV infection with a specific HPV type was an indicator of incident high grade lesions among young women in the general populationThe association between persistence and high grade cervical lesions was more pronounced among women aged over 25
PMCID: PMC124551  PMID: 12228133
19.  Risk of Cervical Pre-Cancer and Cancer Among HIV-Infected Women With Normal Cervical Cytology and No Evidence of Oncogenic HPV Infection 
Context
U.S. cervical cancer screening guidelines for HIV-uninfected women 30 years of age and older have recently been revised, increasing the suggested interval between Pap tests from three years to five years among those with normal cervical cytology (the Pap test) who test negative for oncogenic human papillomavirus (HPV). Whether a three-year or five-year screening interval might be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown.
Objective
To determine the risk of cervical pre-cancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as two separate endpoints, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test and were negative for oncogenic HPV.
Design, Setting and Participants
Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional cohort, between October 1, 2001 and September 30, 2002, with follow-up through April 30, 2011. Clinical sites were in the Bronx, Brooklyn, Chicago, Los Angeles, San Francisco, and Washington, DC. Semi-annual visits included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using PCR. The primary analysis was truncated at five years of follow-up.
Main Outcome Measure
The five-year cumulative incidence of cervical pre-cancer and cancer.
Results
No oncogenic HPV was detected in 369 (88%; 95% CI, 84%-91%) of the HIV-infected women and 255 (91%; 95% CI, 88%-94%) of the HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women two cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500/μL or greater. Histologic data were obtained from four of the six sites. There were six cases of CIN-2+ in N=145 HIV-uninfected women (cumulative incidence = 5% [95% CI, 1%-8%]) and nine cases in N=219 HIV-infected women (cumulative incidence = 5% [95% CI, 2%-8%]). This included one case of CIN-2+ in N=44 oncogenic HPV-negative HIV-infected women with CD4 cell counts less than 350/μL (cumulative incidence = 2% [95% CI, 0%-7%]), one case in N=47 women with CD4 cell counts of 350 to 499/μL (cumulative incidence = 2% [95% CI, 0%-7%]), and seven cases in N=128 women with CD4 cell counts of 500/μL or greater (cumulative incidence = 6% [95% CI, 2%-10%]). One HIV-infected and one HIV-uninfected woman had CIN-3, but none had cancer.
Conclusion
The five-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.
doi:10.1001/jama.2012.5664
PMCID: PMC3556987  PMID: 22820789
20.  Clinical Implications of the Cervical Papanicolaou Test Results in the Management of Anal Warts in HIV-Infected Women 
PLoS ONE  2013;8(11):e81751.
The Papanicolaou test (or Pap test) has long been used as a screening tool to detect cervical precancerous/cancerous lesions. However, studies on the use of this test to predict both the presence and change in size of genital warts are limited. We examined whether cervical Papanicolaou test results are associated with the size of the largest anal wart over time in HIV-infected women in an on-going cohort study in the US. A sample of 976 HIV-infected women included in a public dataset obtained from the Women’s Interagency HIV Study (WIHS) was selected for analysis. A linear mixed model was performed to determine the relationship between the size of anal warts and cervical Pap test results. About 32% of participants had abnormal cervical Pap test results at baseline. In the adjusted model, a woman with a result of Atypia Squamous Cell Undetermined Significance/Low-grade Squamous Intraepithelial Lesion (ASCUS/LSIL) had an anal wart, on average, 12.81 mm2 larger than a woman with normal cervical cytology. The growth rate of the largest anal wart after each visit in a woman with ASCUS/LSIL was 1.56 mm2 slower than that of a woman with normal cervical results. However, they were not significant (P = 0.54 and P = 0.82, respectively). This is the first study to examine the relationship between cervical Pap test results and anal wart development in HIV-infected women. Even though no association between the size of anal wart and cervical Pap test results was found, a screening program using anal cytology testing in HIV-infected women should be considered. Further studies in cost-effectiveness and efficacy of an anal cytology test screening program are warranted.
doi:10.1371/journal.pone.0081751
PMCID: PMC3842937  PMID: 24312348
21.  Abnormal Anal Cytology in HIV-infected Women 
Objective
To assess the prevalence of and risk factors for abnormal anal cytology and HPV infections in HIV-positive women.
Study Design
We conducted an observational single center study of 100 HIV-infected women with cervical and anal specimens obtained for cytology and high risk HPV testing with Hybrid Capture 2.
Results
Seventeen women had abnormal anal cytology, 16 had anal HPV, 21 had abnormal cervical cytology and 24 had cervical HPV. Abnormal anal cytology was associated with cervical HPV infection, abnormal cervical cytology and anal HPV infection in univariate analysis. In multivariate analysis, abnormal anal cytology was associated with CD4 count under 200 cells/mm3, history of STD infection and concurrent cervical cytology abnormality.
Conclusions
HIV-infected women are at high risk for abnormal cytology and HPV infections of both the anus and cervix. Risk factors for abnormal anal cytology include abnormal cervical cytology, cervical and anal HPV infections and low CD4 count.
doi:10.1016/j.ajog.2010.01.010
PMCID: PMC2900418  PMID: 20223443
anal cytology; cervical cytology; anal HPV; cervical HPV; HIV
22.  HPV infection, cervical abnormalities, and cancer in HIV-infected women in Mumbai, India: 12-month follow-up 
Background
HIV-infected women are at a higher risk of cervical intraepithelial neoplasia (CIN) and cancer than women in the general population, partly due to a high prevalence of persistent human papillomavirus (HPV) infection. The aim of the study was to assess the burden of HPV infection, cervical abnormalities, and cervical cancer among a cohort of HIV-infected women as part of a routine screening in an urban overpopulated slum setting in Mumbai, India.
Methods
From May 2010 to October 2010, Médecins Sans Frontières and Tata Memorial Hospital Mumbai offered routine annual Pap smears and HPV DNA testing of women attending an antiretroviral therapy (ART) clinic and a 12-month follow-up. Women with abnormal test results were offered cervical biopsy and treatment, including treatment for sexually transmitted infections (STIs).
Results
Ninety-five women were screened. Median age was 38 years (IQR: 33–41); median nadir CD4-count 143 cells/μL (IQR: 79–270); and median time on ART 23 months (IQR:10–41). HPV DNA was detected in 30/94 women (32%), and 18/94 (19%) showed either low-grade or high-grade squamous intraepithelial lesions (LSIL/HSIL) on Pap smear. Overall, >50% had cervical inflammatory reactions including STIs. Of the 43 women with a cervical biopsy, eight (8.4%) had CIN-1, five (5.3%) CIN-2, and two (2.1%) carcinoma in situ. All but one had HPV DNA detected (risk ratio: 11, 95% confidence interval: 3.3–34). By October 2011, 56 women had completed the 12-month follow-up and had been rescreened. No new cases of HPV infection/LSIL/HSIL were detected.
Conclusion
The high prevalence of HPV infection, STIs, and cervical lesions among women attending an ART clinic demonstrates a need for routine screening. Simple, one-stop screening strategies are needed. The optimal screening interval, especially when resources are limited, needs to be determined.
doi:10.2147/IJWH.S47710
PMCID: PMC3746789  PMID: 23976867
HIV/AIDS; HPV; women’s health; cervical cancer; operational research; India
23.  A Community-based Cervical Cancer Screening Program among Women of Delhi using Camp Approach 
Background:
Cervical cancer is the commonest malignancy among women in developing countries. Cytological screening (Pap smear) have been claimed to reduce incidence and mortality of carcinoma cervix significantly for which sensitization of women is required through community-based approach.
Objectives:
To find out number of cervical cancer cases among patients reporting to a general health care camp through screening program and study the prevalence of perceived morbidity and its confirmation.
Settings:
Cross-sectional study among women attending cancer awareness camps.
Materials and Methods:
A total of 435 women attending cancer awareness camps were screened for carcinoma cervix. The findings of history and clinical examination were recorded. Pap smears of all the symptomatic patients were collected and cytological diagnosis was confirmed by a pathologist.
Results and Conclusions:
The perceived gynecological morbidity was observed to be 59.8%. The smear of the women who were suspected of carcinoma on clinical examination was confirmed to be the cases of carcinoma-in-situ (7.8%) and high-grade neoplasia (2.9%) on laboratory investigations. The findings of the study highlight the utility and need of cancer cervix screening among the women at regular intervals through camp approach in the community.
doi:10.4103/0970-0218.62576
PMCID: PMC2888376  PMID: 20606928
Camp approach; cancer cervix; community-based; screening
24.  Outcome of "Atypical Squamous Cells" in Cervical Cytology: Follow-up Assessment by Loop Electrical Excision Procedure 
Korean Journal of Pathology  2012;46(4):359-364.
Background
We have retrospectively assessed the incidence and outcome of women diagnosed during a hospital-based cytology screening program with "atypical squamous cells (ASC)" and followed-up with loop electrical excision procedure (LEEP).
Methods
We analyzed 173,947 cases of cervical smears' follow-up cytology and histology findings. Previous or archival cytology with LEEP results were retrieved for 390 women with ASC of undetermined significance (ASC-US) and 112 with ASC, cannot exclude high-grade squamous intraepithelial lesion (ASC-H).
Results
On the follow-up cytology, of the 390 women initially diagnosed with ASC-US, 130 (33.3%) had no follow-up records of smears before LEEP; smears of 18 (4.6%) were negative for cytologic abnormalities, 193 (49.5%) were ASC-US, 24 (6.2%) were ASC-H, 111 (28.5%) were low grade squamous intraepithelial lesion (SIL), and 44 (11.4%) were high grade SIL. LEEP findings in these 390 women showed that 183 (46.9%) were negative, 73 (18.7%) were graded as cervical intraepithelial neoplasia (CIN) 1, 25 (6.4%) as CIN 2, 102 (26.2%) as CIN 3, and 7 (1.8%) had carcinoma. LEEP was performed in 112 women initially diagnosed with ASC-H; 36 (32.1%) were negative, 4 (3.6%) were graded as CIN 1, 7 (6.3%) as CIN 2, 60 (53.6%) as CIN 3, and 5 (4.5%) with carcinoma.
Conclusions
Patients with ASC-H smears were at increased risk of SIL or carcnoma compared with patients with ASC-US. Careful follow-up is required in ASC patients.
doi:10.4132/KoreanJPathol.2012.46.4.359
PMCID: PMC3479825  PMID: 23110028
Cervix uteri; Cytology; Loop electrical excision procedure; Atypical squamous cell
25.  Validation of Cervical Cancer Screening Methods in HIV Positive Women from Johannesburg South Africa 
PLoS ONE  2013;8(1):e53494.
Background
HIV-infected women are at increased risk for developing cervical cancer. Women living in resource-limited countries are especially at risk due to poor access to cervical cancer screening and treatment. We evaluated three cervical cancer screening methods to detect cervical intraepithelial neoplasia grade 2 and above (CIN 2+) in HIV-infected women in South Africa; Pap smear, visual inspection with 5% acetic acid (VIA) and human papillomavirus detection (HPV).
Methods
HIV-infected women aged 18–65 were recruited in Johannesburg. A cross-sectional study evaluating three screening methods for the detection of the histologically-defined gold standard CIN-2 + was performed. Women were screened for cervical abnormalities with the Digene HC2 assay (HPV), Pap smear and VIA. VIA was performed by clinic nurses, digital photographs taken and then later reviewed by specialist physicians. The sensitivity, specificity and predictive valves for CIN-2 + were calculated using maximum likelihood estimators.
Results
1,202 HIV-infected women participated, with a median age of 38 years and CD4 counts of 394 cells/mm3. One third of women had a high grade lesion on cytology. VIA and HPV were positive in 45% and 61% of women respectively. Estimated sensitivity/specificity for HPV, Pap smear and VIA for CIN 2+ was 92%/51.4%, 75.8%/83.4% and 65.4/68.5% (nurse reading), respectively. Sensitivities were similar, and specificities appeared significantly lower for the HPV test, cytology and VIA among women with CD4 counts ≤200 cells/mm3 as compared to CD4 counts >350 cells/mm3.
Conclusions
Although HPV was the most sensitive screening method for detecting CIN 2+, it was less specific than conventional cytology and VIA with digital imaging review. Screening programs may need to be individualized in context of the resources and capacity in each area.
doi:10.1371/journal.pone.0053494
PMCID: PMC3543403  PMID: 23326441

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