Persistent Human Papillomavirus Infection as a Predictor of Cervical Intraepithelial Neoplasia

TLDR

Human papillomavirus is the primary cause of cervical cancer, yet most evidence comes from retrospective studies that lack insight into the cumulative or persistent exposure dynamics. This study aimed to evaluate the risk of cervical neoplasia associated with prior persistent HPV infections. A longitudinal cohort of 1,611 women in São Paulo, Brazil, was followed from 1993 to 2000 with HPV testing and Pap smears every four months in the first year and biannually thereafter. Persistent oncogenic HPV infection, particularly types 16 and 18, increased the incidence of cervical intraepithelial lesions from 0.73 to 8.68 per 1000 women‑months and raised the relative risk of any SIL to 10.19 and high‑grade SIL to 11.67.

Abstract

ContextHuman papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection.ObjectiveTo assess the risks of cervical neoplasia related to prior persistent HPV infections.Design and SettingLongitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of São Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000.ParticipantsA total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits.Main Outcome MeasureCervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears.ResultsThe incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18.ConclusionA strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.