Genital HPV infection and E7mRNA viral load: Incidence, risk factors, and relations to genital neoplasias

The goals of this longitudinal study were to investigate risk factors for (1) HPV acquisition and (2) high viral load and (3) define the relationships between viral loads and development of HPV-related lesions in a population of female university students. Triannual gynecologic visits included collection of cervical and vulvovaginal specimens for HPV and Pap testing. The epidemiology of HPV infections is reviewed in chapter 1. The focus of chapter 2 was to evaluate whether male condoms reduce the risk of male-to-female HPV transmission. Analyses were restricted to 145 female university students reporting their first intercourse with a male partner while on study or within 3 months of enrollment. Every two weeks, women completed electronic diaries designed to capture daily information on sexual behaviors, including numbers of sex acts and condom use. The 12-month cumulative incidence of HPV infection associated with a first sex partner was 26.9% (95% confidence interval (CI)=19.1--36.9). Women using condoms for all sex acts during the past 8 months were significantly less likely to acquire an incident infection than women reporting less than 5% condom use (hazard ratio (HR)=0.28, 95%CI=0.12--0.68), after adjusting for new partners and male partners' lifetime numbers of previous partners. Among newly sexually active women, consistent condom use appears to reduce the risk of HPV infection. In chapter 3 we used a quantitative real-time reverse-transcription PCR assay to measure HPV 16 and 18 E7 mRNA viral loads in 47 female university students with incident type-specific HPV DNA infections. Increasing HPV 16 (but not HPV 18) viral load was associated with an increased risk of developing cervical squamous intraepithelial lesions (SIL) (HR per 1 log increase in viral load=2.01, 95% CI=1.45--2.78, adjusted for concurrent detection of other HPV DNA types). Current smoking was associated with decreased viral load (odds ratio associated with 1 log increase in viral load=0.21, 95% CI=0.05--0.97, adjusted for number of new partners). In the era of prophylactic HPV vaccines, RNA levels may provide a useful indicator of the clinical importance of break-through infections.