||Plummer M, Peto J, Franceschi S, International Collaboration of Epidemiological Studies of Cervical Cancer, Rajkumar T, Cuzick J, Appleby P, Beral V, Berrington de González A, Bull D, Canfell K, Crossley B, Green J, Reeves G, Sweetland S, Kjaer S, Painter R, Vessey M, Daling J, Madeleine M, Ray R, Thomas DB, Herrero R, Ylitalo N, Bosch FX, Castellsagué X, de Sanjosé S, Louie K, Moreno V, Hammouda D, Negri E, Alvarez M, Galdos O, Santos C, Velarde C, Muñoz N, Franceschi S, Plummer M, Peto J, Dillner J, Silins I, Bayo S, Chaouki N, Rolón PA, Brinton L, Castle P, Hildesheim A, Lacey J Jr, Schiffman M, Stein L, Urban MI, Hannaford P, Chichareon SB, Sitas F, Eluf-Neto J, La Vecchia C, Skegg D, Peters R, Pike MC, Ursin G, Ngelangel C, Gram IT, Farley T, Meirik O
||Young age at first sexual intercourse (AFI) is an important risk factor for cervical cancer, but no simple statistical model of its influence has been established. We investigated the relationship between risk of cervical carcinoma and time since first intercourse using data on monogamous women (5,074 cases and 16,137 controls) from the International Collaboration of Epidemiological Studies of Cervical Cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from pooled data on 20 studies using conditional logistic regression. The OR for invasive cervical carcinoma is approximately proportional to the square of time since first intercourse (exponent 1.95, 95% CI: 1.76-2.15) up to age 45. First cervical infection with human papillomavirus (HPV) often occurs soon after first sexual intercourse, so early AFI is a reasonable proxy for early age at first exposure to HPV. In addition, age-specific incidence rates of cervical cancer in unscreened populations remain fairly constant above age 45. Cervical cancer thus resembles other cancers caused by strong early-stage carcinogens, with incidence rates proportional to a power of time since first exposure and also resembles cancers of the breast and other hormone-dependent epithelia, where a similar flattening of age-specific incidence rates is seen at the time menopausal changes start. Taken together, these observations suggest that HPV vaccination may prevent the majority of cervical cancers by delaying HPV infection without necessarily providing lifetime protection against HPV.