The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy=biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p 5 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments. ' 2005 Wiley-Liss, Inc.Key words: visual inspection with acetic acid; cytology; human papillomavirus testing; cervical cancer; screening Cervical cancer is an important public health problem of adult women in many developing countries. 1,2 Cytology screening programs have resulted in a marked decline of this disease in developed countries. 2 However, the considerable financial, technical and logistic inputs necessary for effective cytology programs means that the results obtained in developing countries have been, at best, mediocre. 3,4 Hence, it is important to evaluate the effectiveness of alternative methods of screening, such as VIA and HPV testing, that may be more readily implemented in different settings.VIA is simple and inexpensive and can be provided by midwives, nurses and other HWs. Its accuracy at detecting cervical neoplasia has been extensively studied and found to be satisfactory. [5][6][7] The role of persistent infection with oncogenic types of HPV in the etiology of cervical cancer has encouraged the evaluation of HPV testing as a screening tool. [8][9][10] The ultimate proof of efficacy of a screening test for cervical neoplasia is its ability to prevent invasive cancer when implemented in a program setting. Whether a screening program using VIA or HPV testing will be followed by a reduction in disease burden and the cost-effectiveness of these alternate approaches based on real program-based information remain to be established. These appro...