Adolescents and HIV

Causes of High-Grade Squamous Intraepithelial Lesion in HIV-Infected Adolescents

Study Question(s): What is the risk of developing human papillomavirus (HPV)-associated precancer high-grade squamous intraepithelial lesion (HSIL) among adolescents with and without HIV infection? What co-factors are associated with developing HSIL?

Study Participants: 172 HIV-infected and 84 HIV-uninfected adolescent girls enrolled in a prospective, multicenter study of HIV infection among adolescents with high-risk sexual behaviors (the REACH study). Girls were enrolled at 15 clinical sites across the U.S. from February 1996 through September 1999. Follow-up ended in November 2000.

Study Methods: Clinical and laboratory data were collected at baseline and at 6 month intervals, with an average of 6.59 follow up visits for HIV-infected subjects and 6.30 visits for HIV-uninfected subjects. The presence of HSIL and precancer low-grade squamous intraepithelial lesion (LSIL) was based on cytologic diagnosis.

Study Findings: At baseline, the presence of HSIL did not differ by HIV status. However, HIV infection was associated with a greater incidence of HSIL in girls who were HSIL negative at baseline. In looking at predictors of HSIL, the researchers found that presence of persistent LSIL was a large risk factor for developing HSIL. About three-quarters (78%) of subjects who developed HSIL had a preceding diagnosis of LSIL. In fact, multivariate analyses showed that persistent LSIL was an important factor in the relationship between HIV infection and greater incidence of HSIL. Other factors associated with greater risk of HSIL were HPV infection, high IL-2 levels in cervical mucous, and use of hormonal contraceptives. CD4 immunosupression did not contribute HSIL risk when other factors were controlled.

Limitations: The adolescents in the study were already in primary care which excluded individuals who may have been at the highest risk for HSIL. Also, diagnoses were based on cytologic examination so rates of HSIL may be greater than those obtained with biopsy.

Lessons Learned: This study showed that the rate of HSIL in HIV-infected adolescent girls was 3-4 times greater than rates reported for adult women. The findings also point to persistent LSIL as the important factor in developing HSIL, rather than persistent HPV infection-which does not always produce LSIL. Importantly, the observed association between hormonal contraceptives and HSIL is a potential concern in young women with limited exposure to these drugs and should be further investigated. The high rates of HSIL as well as the high rate of progression from LSIL to HSIL highlight the importance of regular gynecologic care and monitoring of HIV-infected adolescents. In addition, limitations of available treatment coupled with the incidence of LSIL underscore the need for new therapies.

Source: Moscicki, AB., Ellenberg, JH., Crowley-Nowick, P., Darragh, TM., Xu, J., and Fahrat, S. Risk of high-grade squamous intraepithelial lesion in HIV-infected adolescents. Journal of Infectious Diseases. 2004 October: 190(8). 1413-21.