Risk Factors for Low-Grade Cervical Abnormalities Differ from Those for Human Papillomavirus Infection

-D. Hollander

First published online:

A type of benign lesion commonly thought to be caused by infection with the human papillomavirus (HPV) appears to have a set of risk factors distinct from those associated with the acquisition of HPV.1 In a prospective study conducted among family planning clinic patients in San Francisco, when all relevant factors were taken into account, HPV risk was influenced by sexual behavior, infection history and pill use; the risk of developing low-grade squamous intraepithelial lesions, by contrast, was associated with HPV infection and cigarette smoking. Furthermore, one in four women who were HPV-infected at entry to the study developed lesions during the follow-up period.

The study cohort consisted of 13-20-year-old women attending two family planning clinics for HPV testing between 1990 and 1994. At baseline and follow-up visits, women were tested for HPV and cervical abnormalities, and were interviewed about their sexual behaviors and substance use. Follow-up visits were scheduled every four months for women with HPV infection and every six months for those who were HPV-negative. The median duration of follow-up was 50 months, and the median number of visits made was nine.

To assess the factors associated with acquisition of HPV, the researchers examined data on 105 women who tested negative for the virus both at baseline and at the first follow-up visit. Analyses of the factors that increase the risk of developing low-grade squamous intraepithelial lesions were based on 496 women who were HPV-infected at baseline or tested positive later in the follow-up period. Fifty-four women who became infected with HPV during follow-up were included in both sets of analyses. Women in the study of HPV risk had had significantly fewer sexual partners than those in the segment of the cohort used to examine the risk of lesions (median, three vs. five), but the two groups were similar with regard to other sexual behavior factors, history of chlamydia or gonorrhea, age, race and socioeconomic status.

In univariate analyses, the risk of acquiring HPV increased as a woman's number of lifetime partners, number of recent partners and monthly number of new partners increased. It also was elevated among women who had had genital herpes or vulvar warts and among those who had ever smoked marijuana; the risk was reduced among current users of the pill. When the researchers conducted multivariate analyses, controlling for the factors that were significant at the univariate level, most of these factors remained significant predictors of risk. For each new partner a woman had acquired per month, her HPV risk rose dramatically (relative hazard, 10.1). A history of herpes or vulvar warts also continued to be associated with an increased risk (3.5 and 2.7, respectively), and pill users continued to have a lower risk than women not using this method of contraception (0.5).

Of the 496 women in the study of risk factors for low-grade lesions, 109--about one in four--developed lesions during the follow-up period. Univariate analyses suggested that HPV infection was the strongest predictor of this condition, and the risk roughly doubled with each year that a woman was infected with any given type of the virus. Daily cigarette smoking and both current use and ever-use of marijuana also were associated with an increased risk of developing lesions. Again, the multivariate calculations by and large confirmed the univariate results. Women who had had HPV for intervals up to three years had sharply increased risks of lesions (relative hazards, 6.1-10.3); those who smoked cigarettes daily also had an elevated risk (1.7).

Summarizing their findings, the researchers note that they observed "clear differences" in the risk factors for these two conditions, and that while lesion development was strongly associated with HPV infection, it also hinged on the presence of other risk factors. Thus, they conclude that many of the factors that have previously been associated with low-grade squamous intraepithelial lesions were "either risk factors for or surrogate markers of HPV infection."--D. Hollander


1. Moscicki A-B et al., Risks for incident human papillomavirus infection and low-grade squamous intra- epithelial lesion development in young females, Journal of the American Medical Association, 2001, 285(23): 2995-3002.