Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females.

ContextLow-grade squamous intraepithelial lesions(LSILs) have been described as a benign cytological consequence of active human papillomavirus (HPV) replication. Several studies have reported that certain behavioral and biological risks exist for LSIL, suggesting that HPV alone is not sufficient for the development of LSIL. However, because most of these studies have been cross-sectional, it is not known whether behavioral and biological risks are simply risks for HPV infectionitself.ObjectiveTo prospectively examine risks of incident HPV infectionin HPV-negative females and of incident LSIL development in females with HPV infection.DesignProspective cohort study conducted between 1990-2000, with a median follow-up of 50 months.Setting and ParticipantsFemales aged 13 to 21 years who attended 2 family planning clinics in the San Francisco bay area; 496 had prevalent HPV infectionand 105 were HPV-negative.Main Outcome MeasureIncident development of HPV infectionand LSIL, analyzed by various demographic, behavioral, and clinical risk factors.ResultsFifty-four incident HPV infectionsoccurred in the 105 females who were HPV-negative at study entry (median duration of follow-up for those who remained HPV-negative was 26 months). Multivariable analysis showed that risks of HPV included sexual behavior (relative hazard [RH], 10.10; 95% confidence interval [CI], 3.24-31.50 per new partner per month), history of herpes simplex virus (RH, 3.54; 95% CI, 1.37-9.10), and history of vulvar warts (RH, 2.73; 95% CI, 1.27-5.87). Current use of oral contraceptives had a significantly protective effect (RH, 0.49; 95% CI, 0.28-0.86). Among the 496 individuals who were HPV-positive at baseline or in follow-up, there were 109 incident cases of LSIL during the follow-up interval, with a median fo llow-up time of60 months for those who never developed LSIL. Human papillomavirus infection was the most significant risk factor for development of LSIL. The multivariable model showed the following risks for LSIL: HPV infectionfor less than 1 year (RH, 7.40; 95% CI, 4.74-11.57); HPV infectionfor 1 to 2 years (RH, 10.27; 95% CI, 5.64-18.69); HPV infectionfor 2 to 3 years (RH, 6.11; 95% CI, 1.86-20.06); and daily cigarette smoking (RH, 1.67; 95% CI, 1.12-2.48).ConclusionOur results indicate distinct risks for HPV and LSIL. In addition, most women with HPV infectionin our study did not develop LSIL within a median follow-up period of 60 months. These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are, in fact, risks for acquisition of HPV. Cigarette smoking was a risk specific to LSIL, supporting the role of tobacco in neoplastic development.