Objective: To compare performance of conventional Pap test, liquid-based cytology (LBC) and visual inspection with acetic acid (VIA), as well as human papillomavirus (HPV) testing in 2 subcohorts of women, < 35 and ≥ 35 years of age. Study Design: Performance indicators were calculated using colposcopic biopsies as the gold standard; all results were corrected for verification bias using maximum likelihood. Results: Both conventional Pap test and Hybrid Capture 2 (HC2) assay performed significantly better among older women than younger; no difference was observed in performance of LBC and VIA, both inferior to Pap and HC2. The Pap test was more specific than HC2 in both subcohorts; HC2 had the highest sensitivity. For individual tests, the best balance between sensitivity and specificity was obtained for HC2 assay corrected for verification bias in the older women's subcohort; this was further improved by the combined use of the Pap test and HC2. Conclusion: Age of the target population is an important determinant of the performance of different screening tests. The choice of optimal test for women < 35 and ≥ 35 years of age depends on whether the highest positive predictive value (Pap test) or the best SE/SP balance (HC2) is used as the selection criterion. © The International Academy of Cytology.526641653Syrjänen, K., Early detection of CIN and HPV: Prevention of cervical cancer (2000) Papillomavirus Infections in Human Pathology, pp. 167-188. , Edited by K Syrjänen, S Syrjänen. New York, J Wiley & SonsMiller, A.B., Nazeer, S., Fonn, S., Brandup-Lukanow, A., Rehman, R., Cronje, H., Sankaranarayanan, R., Onsrud, M., Report on Consensus Conference on Cervical Cancer Screening and Management, , Int J Cancer 200086:440-447Hakama, M., Screening for cervical cancer: Experience from the Nordic Countries (1997) New Developments in Cervical Cancer Screening and Prevention, pp. 190-199. , Edited by E Franco, J Monsonego. Oxford, Blackwell ScienceMonsonego, J., HPV infections and cervical cancer prevention: Priorities and new directions (2005) Gynecol Oncol, 96, pp. 830-839Monsonego, J., Bosch, F.X., Coursaget, P., Cox, J.T., Franco, E., Frazer, I., Sankaranaraynanan, R., Meijer, C., Cervical cancer control, priorities and new directions (2004) Int J Cancer, 108, pp. 329-333Anttila, A., Nieminen, P., Cervical cancer screening programme in Finland with an example on implementing alternative screening methods (2007) Coll Anthropol, 31 (SUPPL. 2), pp. 17-22(1987) Papillomaviruses and Human Disease, pp. 1-518. , Syrjänen K, Gissmann L, Koss LG editors, Berlin, Heidelberg, Springer Verlag(2003) Papillomavirus Humains: Biologie et Pathologie Tumorale, pp. 1-759. , Aubin F, Pretet JL, Mougin C editors, Paris, Editions TEC & DOC(2006) Papillomavirus Research: From Natural History to Vaccines and Beyond, pp. 1-424. , Campo S editor, Norwich, U.K, Caister Academic PressLorincz, A.T., Richart, R.M., Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs (2003) Arch Pathol Lab Med, 127, pp. 959-968Arbyn, M., Buntinx, F., Van Ranst, M., Paraskivaidis, E., Martin-Hirsch, P., Dillner, J., Virologic versus cytologic triage of women with equivocal Pap smears: A meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia (2004) J Natl Cancer Inst, 96, pp. 280-293Koss, L.G., Performance of cytology in screening for precursor lesions and early cancer of the uterine cervix (1997) New Developments in Cervical Cancer Screening and Prevention, pp. 147-150. , Edited by E Franco, J Monsonego. Oxford, Blackwell ScienceNanda, K., McCrory, D.C., Myers, E.R., Bastian, L.A., Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: A systematic review (2000) Ann Intern Med, 132, pp. 810-819Wright Jr, T.C., Schiffman, M., Solomon, D., Cox, J.T., Garcia, F., Goldie, S., Hatch, K., Saslow, D., Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening (2004) Obstet Gynecol, 103, pp. 304-309Ferris, D.G., The 2001 ASCCP management guidelines for cervical cytology (2004) Am Fam Physician, 70, pp. 1866-1868Cox, T., Cuzick, J., HPV DNA testing in cervical cancer screening: From evidence to policies (2006) Gynecol Oncol, 103, pp. 8-11Franco EL, Bosch FX, Cuzick J, Schiller JT, Garnett GP, Meheus A, Wright TC: Knowledge gaps and priorities for research on prevention of HPV infection and cervical cancer. Vaccine (Supp 13) 2006;24:S242-S249Cuzick, J., Beverley, E., Ho, L., Terry, G., Sapper, H., Mielzynska, I., Lorincz, A., Soutter, P., HPV testing in primary screening of older women (1999) Br J Cancer, 81, pp. 554-558Clavel, C., Masure, M., Bory, J.P., Putaud, I., Mangeonjean, C., Lorenzato, M., Nazeyrollas, P., Birembaut, P., Human papillomavirus testing in primary screening for the detection of high-grade cervical lesions: A study of 7932 women (2001) Br J Cancer, 84, pp. 1616-1623Duttagupta, C., Sengupta, S., Roy, M., Sengupta, D., Chakraborty, S., Bhattacharya, P., Roy, S., Ghosh, S., Oncogenic human papillomavirus (HPV) infection and uterine cervical cancer: A screening strategy in the perspective of rural India (2002) Eur J Cancer Prev, 11, pp. 447-456Goldie, S.J., Kim, J.J., Wright, T.C., Cost-effectiveness of human papillomavirus DNA testing for cervical cancer screening in women aged 30 years or more (2004) Obstet Gynecol, 103, pp. 619-631Holmes, J., Hemmett, L., Garfield, S., The cost-effectiveness of human papillomavirus screening for cervical cancer: A review of recent modelling studies (2005) Eur J Health Econ, 6, pp. 30-37Ronco, G., Giorgi-Rossi, P., Carozzi, F., Dalla Palma, P., Del Mistro, A., De Marco, L., De Lillo, M., Cuzik, J., New Technologies for Cervical Cancer Screening Working Group: Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 3 5 years: Results at recruitment for a randomised controlled trial (2006) Lancet Oncol, 7, pp. 547-555Kitchener, H.C., Almonte, M., Wheeler, P., Desai, M., Gilham, C., Bailey, A., Sargent, A., Peto, J., ARTISTIC Trail Study Group: HPV testing in routine cervical screening: Cross sectional data from the ARTISTIC trial (2006) Br J Cancer, 95, pp. 56-61Wiley, D.J., Monk, B.J., Masongsong, E., Morgan, K., Cervical cancer screening (2004) Curr Oncol Rep, 6, pp. 497-506Baay, M.F., Tjalma, W.A., Lambrechts, H.A., Pattyn, G.G., Lardon, F., Weyler, J., Van Royen, P., Vermorken, J.B., Combined Pap and HPV testing in primary screening for cervical abnormalities: Should HPV detection be delayed until age 35? (2005) Eur J Cancer, 41, pp. 2704-2708Agorastos, T., Dinas, K., Lloveras, B., de Sanjose, S., Komegay, J.R., Bond, H., Bosch, F.X., Bonds, J., Human papillomavirus testing for primary screening in women at low risk of developing cervical cancer: The Greek experience (2005) Gynecol Oncol, 96, pp. 714-720Ronco, G., Cuzick, J., Segnan, N., Brezzi, S., Carozzi, F., Folicaldi, S., Dalla Palma, P., Giorgi-Rossi, P., NTCC Working Group: HPV triage for low grade (L-SIL) cytology is appropriate for women over 35 in mass cervical cancer screening using liquid based cytology (2007) Eur J Cancer, 43, pp. 476-480Syrjänen, K., Naud, P., Derchain, S.M., Roteli-Martins, C., Longatto-Filho, A., Tatti, S., Branca, M., Syrjänen, S., Comparing PAP smear cytology, aided visual inspection, screening colposcopy, cervicography and HPV testing as optional screening tools in Latin America: Study design and baseline data of the LAMS Study (2005) Anticancer Res, 25, pp. 3469-3480Longatto-Filho, A., Maeda, M.Y., Erzen, M., Branca, M., Roteli-Martins, C., Naud, P., Derchain, S.F., Syrjänen, K., Conventional Pap smear and liquid-based cytology as screening tools in low-resource settings in Latin America: Experience of the Latin American Screening Study (2005) Acta Cytol, 49, pp. 500-506Sarian LO, Derchain SF, Naud P, Roteli-Martins C, Longatto-Filho A, Tatti S, Branca M, Erzen M, Serpa-Hammes L, Matos J, Gontijo R, Bragança JF, Lima TP, Maeda MY, Lörincz A, Dores GB, Costa S, Syrjänen S, Syrjänen K: Evaluation of visual inspection with acetic acid (VIA), Lugol's iodine (VILI) cervical cytology and HPV testing as cervical screening tools in Latin America: This report refers to partial results from the LAMS (Latin AMerican Screening) study. J Med Screen 2005;12:142-149Longatto-Filho, A., Erzen, M., Branca, M., Roteli-Martins, C., Naud, P., Derchain, S.F., Hammes, L., Syrjänen, K., Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: Experience from the Latin American Screening Study (2006) Int J Gynecol Cancer, 16, pp. 955-962Hammes, L.S., Naud, P., Passos, E., Matos, J., Brouwers, K., Rivoire, W., Syrjänen, K.J., Value of the International Federation of Colposcopy and Cervical Pathology (IFCPC) terminology in predicting cervical pathology (2007) J Lower Genital Tract Dis, 11, pp. 158-165Seed, P.T., Tobias, A., Summary statistics for diagnostic tests (2001) Stata Techn Bull, 59, pp. 9-12Alonzo, T.A., Verification bias-corrected estimators of the relative true and false positive rates of two binary screening tests (2005) Stat Med, 24, pp. 403-417Reichenheim, M.E., Ponce de Leon, A., Estimation of sensitivity and specificity arising from validity studies with incomplete designs (2002) Stata J, 2, pp. 267-279Koliopoulos, G., Arbyn, M., Martin-Hirsch, P., Kyrgiou, M., Prendiville, W., Paraskevaidis, E., Diagnostic accuracy of human papillomavirus testing in primary cervical screening: A systematic review and meta-analysis of non-randomized studies (2007) Gynecol Oncol, 104, pp. 232-246Petignat, P., Faltin, D., Goffin, F., Bilieux, M.H., Stucki, D., Sporri, S., Vassilakos, P., Age-related performance of human papillomavirus testing used as an adjunct to cytology for cervical carcinoma screening in a population with a low incidence of cervical carcinoma (2005) Cancer, 105, pp. 126-132Syrjänen, S., Shabalova, I., Petrovichev, N., Podistov, J., Ivanchenko, O., Zakharenko, S., Nerovjna, R., Syrjänen, K., NIS Cohort Study Group: Age-specific incidence and clearance of high-risk human papillomavirus infections in women in the former Soviet Union (2005) Int J STD AIDS, 16, pp. 217-223Clavel, C., Bory, J.P., Rihet, S., Masure, M., Duval-Binninger, I., Putaud, I., Lorenzato, M., Birembaut, P., Comparative analysis of human papillomavirus detection by hybrid capture assay and routine cytologic screening to detect high-grade cervical lesions (1998) Int J Cancer, 75, pp. 525-528Kuhn, L., Denny, L., Pollack, A., Lorincz, A., Richart, R.M., Wright, T.C., Human papillomavirus DNA testing for cervical cancer screening in low-resource settings (2000) J Natl Cancer Inst, 92, pp. 818-825Salmeron, J., Lazcano-Ponce, E., Lorincz, A., Hernández, M., Hernández, P., Levya, A., Uribe, M., Shah, K.V., Comparison of HPV-based assays with Papanicolaou smears for cervical cancer screening in Morelos State, Mexico (2003) Cancer Causes Control, 14, pp. 505-512Moss, S., Gray, A., Legood, R., Vessey, M., Patnick, J., Kitchener, H., Effect of testing for human papillomavirus as a triage during screening for cervical cancer: Observational before and after study (2006) BMJ, 332, pp. 83-85. , Liquid-Based Cytology Human Papillomavirus Cervical Studies GroupMiranda Pereira, S.M., Castelo, A., Makabe, S., Utagawa, M.L., Di Loreto, C., Sakamoto Maeda, M.Y., Margues, J.A., Das Dores, G.B., Screening for cervical cancer in high-risk populations: DNA Pap test or Hybrid Capture II test alone? (2006) Int J Gynecol Pathol, 25, pp. 38-41Shastri, S.S., Dinshaw, K., Amin, G., Goswami, S., Patil, S., Chinoy, R., Kane, S., Sankaranarayanan, R., Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India (2005) Bull World Health Organ, 83, pp. 186-194Sankaranarayanan, R., Nene, B.M., Dinshaw, K.A., Mahe, C., Jayant, K., Shastri, S.S., Malvi, S.G., Panse, N., Osmanabad District Cervical Screening Study Group: A cluster randomized controlled trial of visual, cytology and human papillomavirus screening for cancer of the cervix in rural India (2005) Int J Cancer, 116, pp. 617-623dos Santos Silva, I., (1999) Cancer Epidemiology: Principles and Methods, pp. 355-383. , Lyon, IARC Press