The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectional studies with common protocol and questionnaire in 3 different locations (Kolkata, Mumbai and Trivandrum) in India. These studies involved 18,085 women aged 25-65 years. The reference standard for final diagnosis was a combination of colposcopy/biopsy. All women were investigated with colposcopy and 3,116 received directed biopsy. The sensitivity of HPV testing for detecting CIN 2-3 lesions varied from 45.7% to 80.9% across the study sites; the specificity varied from 91.7% to 94.6% and the positive predictive value from 6.7% to 13.7%. Retesting of 298 randomly chosen denatured samples in France revealed an agreement rate of 85.9% and a -value of 0.72. Although HPV testing seems to be a promising approach for cervical cancer prevention, a large range in sensitivity was observed in our study, possibly due to variations in the quality of specimen collection and reference standards. A higher sensitivity was associated with the center performing the test well. Further developments in terms of more reproducible, less expensive and less sophisticated testing are essential to make the test feasible and effective in low-resource settings. © 2004 Wiley-Liss, Inc. II; accuracy; sensitivity; specificity; cervical neoplasia; screening; prevention It has been well established that cervical neoplasia are caused by persistent infection with certain oncogenic types of human papillomaviruses (HPVs). 1,2 This knowledge has led to the evaluation of potential applications in the prevention of cervical cancer such as vaccination and its usefulness in the primary screening, in secondary triage and in the follow-up of treated cases of cervical neoplasia. In the setting of primary screening, HPV testing is being evaluated as a potential alternative or adjunctive to cervical cytology for the early detection of cervical cancer precursors and prevention of invasive cervical cancer. HPV testing is intuitively a more objective test than cytology or visual methods, which are based on the interpretation by the readers and are subject to wide interobserver variations. In low-resource settings, where repeated testing of women at risk for cervical neoplasia may not be feasible due to logistic, organizational and financial reasons, HPV testing may provide an objective method of identifying and investing the limited resources on women at risk for disease. Key words: HPV testing; Hybrid captureWe evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method (Digene, Gaithersburg, MD) in detecting cervical intraepithelial neoplasia lesions grade 2 and 3 (CIN 2-3) in 4 cross-sectional studies in 3 different locations in India. This was a joint collaborative project between the Chittaranjan National Cancer Institute (CN...

Visual inspection of the cervix after application of 3-5% acetic acid (VIA) is a potential alternative to cytology for screening in low-resource countries. The present study evaluated the performance of VIA, magnified visual inspection after application of acetic acid (VIAM), and cytology in the detection of high-grade cervical cancer precursor lesions in Kolkata (Calcutta) and suburbs in eastern India. Trained health workers with college education concurrently screened 5881 women aged 30-64 years with VIA, VIAM, and conventional cervical cytology. Detection of well-defined, opaque acetowhite lesions close to the squamocolumnar junction; well-defined, circumorificial acetowhite lesions; or dense acetowhitening of ulceroproliferative growth on the cervix constituted a positive VIA or VIAM. Cytology was considered positive if reported as mild dysplasia or worse lesions. All screened women (N = 5881) were evaluated by colposcopy, and biopsies were directed in those with colposcopic abnormalities (N = 1052, 17.9%). The final diagnosis was based on histology (if biopsies had been taken) or colposcopic findings, which allowed direct estimation of sensitivity, specificity, and predictive values. Moderate or severe dysplasia or carcinoma in situ (CIN 2-3 disease) was considered as true positive disease for the calculation of sensitivity, specificity, and predictive values of screening tests. 18.7%, 17.7% and 8.2% of the women tested positive for VIA, VIAM, and cytology. One hundred twenty two women had a final diagnosis of CIN 2-3 lesions. The sensitivities of VIA and VIAM to detect CIN 2-3 lesions were 55.7% and 60.7%, respectively; the specificities were 82.1% and 83.2%, respectively. The sensitivity and specificity of cytology were 29.5% and 92.3%, respectively. All the tests were associated with negative predictive values above 98%. VIA and VIAM had significantly higher sensitivity than cytology in our study; the specificity of cytology was higher than that of VIA and VIAM.

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Visual inspection after acetic acid application (VIA) and human papillomavirus (HPV) detection tests have been recommended to screen women for cervical cancer in low and middle income countries. A demonstration project in rural India screened 39,740 women with both the tests to compare their accuracies in real population setting. The project also evaluated the model of screening women in the existing primary health care facilities, evaluating the screen positive women with colposcopy (and biopsy) in the same setup and recalling the women diagnosed to have disease for treatment at tertiary center. Accuracy of VIA and HPV test used sequentially was also studied. VIA was performed by trained health workers and Hybrid Capture II (HC II) assay was used for oncogenic HPV detection. Test positivity was 7.1% for VIA and 4.7% for HC II. Detection rate of CIN 31 disease was significantly higher with HC II than VIA. Sensitivities of VIA and HC II to detect 162 histology proved CIN 31 lesions were 67.9 and 91.2%, respectively after adjusting for verification bias. Specificity for the same disease outcome and verification bias correction was 93.2% for VIA and 96.9% for HC II. Triaging of VIA positive women with HPV test would have considerably improved the positive predictive value (4.0 to 37.5% to detect CIN 31) without significant drop in sensitivity. All VIA positive women and 74.0% of HC II positive women had colposcopy. There was high compliance to treatment and significant stage-shift of the screen-detected cancers towards more early stage.A number of cross-sectional and randomized controlled studies have evaluated the test characteristics of Visual inspection with acetic acid (VIA) as well as that of human papillomavirus (HPV) detection for cervical cancer screening in low and medium income countries.1-4 These studies have convincingly established the utility of these tests and their superiority over conventional Pap smear cytology. The evidence regarding their cost-effectiveness is encouraging and the international organizations have also recommended their use in screening programmes. 5,6 Still the adoption of the new technologies for cervical cancer screening is low in the low or middle income countries (LMIC). Most of these countries continue with the opportunistic, low intensity and ineffectual cytology based screening, even though it is feasible for many of them to implement population based cervical cancer screening using either VIA or HPV detection tests. 7,8 The LMICs are quite diverse in terms of their health system capacities even within the countries. They can follow a "cafeteria approach" and choose from different screening tests and various diagnostic and treatment algorithms (single or multiple visit approaches) depending on the available resources and feasibility. Demonstration projects validating the research observations in real population settings and in convergence with the existing health infrastructure have catalyzed the initiation of VIA based cervical cancer screening programmes in some of the L...