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...