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.

The vast majority of invasive cervical carcinomas harbor additional copies of the chromosome arm 3q, resulting in genomic amplification of the human telomerase gene TERC. Here, we evaluated TERC amplification in routinely collected liquid based cytology (LBC) samples with histologically confirmed diagnoses. A set of 78 LBC samples from a Swedish patient cohort were analyzed with a four-color fluorescence in situ hybridization probe panel that included TERC. Clinical follow-up included additional histological evaluation and Pap smears. Human papillomavirus status was available for all cases. The correlation of cytology, TERC amplification, human papillomavirus typing, and histological diagnosis showed that infection with high-risk human papillomavirus was detected in 64% of the LBC samples with normal histopathology, in 65% of the cervical intraepithelial neoplasia (CIN)1, 95% of the CIN2, 96% of the CIN3 lesions, and all carcinomas. Seven percent of the lesions with normal histopathology were positive for TERC amplification, 24% of the CIN1, 64% of the CIN2, 91% of the CIN3 lesions, and 100% of invasive carcinomas. This demonstrates that detection of genomic amplification of TERC in LBC samples can identify patients with histopathologically confirmed CIN3 or cancer. Indeed, the proportion of TERC-positive cases increases with the severity of dysplasia. Among the markers tested, detection of TERC amplification in cytological samples has the highest combined sensitivity and specificity for discernment of low-grade from high-grade dysplasia and cancer.

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...