BackgroundWhile many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness.Methods and FindingsA population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures.ConclusionsWe conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality.

Objectives: Visual inspection of the cervix after acetic acid application (VIA) is widely recommended as the method of choice in cervical cancer screening programs in resource-limited settings because of its simplicity and ability to link with immediate treatment. In testing the effectiveness of VIA, human papillomavirus DNA testing, and Pap cytology in a population-based study in a peri-urban area in Andhra Pradesh, India, we found the sensitivity of VIA for detection of cervical intraepithelial neoplasia grade 2 and worse (CIN2+) to be 26.3%, much lower than the 60% to 90% reported in the literature. We therefore investigated the determinants of VIA positivity in our study population.Methods: We evaluated VIA positivity by demographics and reproductive history, results of clinical examination, and results from the other screening methods.Results: Of the 19 women diagnosed with CIN2+, only 5 were positive by VIA (positive predictive value, 3.1%). In multivariate analysis, VIA positivity (12.74%) was associated with older age, positive Pap smear, visually apparent cervical inflammation, and interobserver variation. Cervical inflammation of unknown cause was present in 21.62% of women. In disease-negative women, cervical inflammation was associated with an increase in VIA positivity from 6.1% to 15.5% (P < 0.001). Among the six gynecologists who performed VIA, the positivity rate varied from 4% to 31%.Conclusions: The interpretation of VIA is subjective and its performance cannot be readily evaluated against objective standards.Impact: VIA is not a robust screening test and we caution against its use as the primary screening test in resource-limited regions.

We found a large number of false-positive readings by visual inspection with acetic acid (VIA) in a study of cervical cancer screening strategies (VIA, human papillomavirus HPV DNA testing, and Pap cytology) in a periurban community in Andhra Pradesh, India. We evaluated whether these false-positive readings might be occurring as a result of infections with Epstein-Barr virus (EBV) or cytomegalovirus (CMV), prevalent latent herpesviruses known to be shed from the female genital tract. While we found that there was no association between VIA results and the presence of EBV or CMV in the cervix, we did find a high prevalence of both viruses: 20% for EBV and 26% for CMV. In multivariate analyses, CMV prevalence was associated with younger age, lack of running water in the home, and visually apparent cervical inflammation. EBV prevalence was associated with older age and a diagnosis of cervical intraepithelial neoplasia grade 1 or greater. The biological and clinical implications of these viruses at the cervix remain to be determined. The strong association between the presence of EBV and cervical disease warrants future exploration to determine whether EBV plays a causal role in disease development or if it is merely a bystander in the process.We conducted a study of cervical cancer screening strategies in a periurban community near Hyderabad in the state of Andhra Pradesh in southern India. Cervical cells were collected from women for cytological and virological investigation, and the cervix was examined with naked eye visual inspection after application of acetic acid (VIA). We found that a positive VIA reading (presence of an acetowhite lesion in the cervical transformation zone) had a surprisingly low sensitivity (26.3%) and moderate specificity (76.4%) for the detection of cervical neoplasia (9,28).Given the large number of false-positive VIA readings, we inquired if these lesions might be occurring as a result of infections with Epstein-Barr virus (EBV) or cytomegalovirus (CMV), prevalent latent herpesviruses which are known to be shed from the female genital tract (2, 6, 14, 21). We also examined whether cervical EBV and CMV detection correlated with either cervical HPV detection or other markers of cervical pathology, since these viruses have been postulated to have a possible cocarcinogenic role with human papillomavirus (HPV) for cervical neoplasia (19, 23). MATERIALS AND METHODSStudy participants. The study subjects were a subpopulation of the CATCH (Community Access to Cervical Health) project, a population-based screening study in a periurban community near Hyderabad, in the state of Andhra Pradesh, India. The CATCH project aimed to enroll all eligible women 25 years of age and older who were not pregnant and who had not had a hysterectomy. A total of 2,331 women, or approximately 40% of those eligible, were enrolled and consented to an interviewer-administered questionnaire to collect data on demographics, reproductive health, cervical cancer screening history, and smoking status. Participants also pr...