Obstetrics and Gynecology: Gynecology
Effect of antiretroviral therapy on the incidence of genital warts and vulvar neoplasia among women with the human immunodeficiency virus☆

https://doi.org/10.1016/j.ajog.2003.12.037Get rights and content

Abstract

Objective

The purpose of this study was to determine the incidence and predictors of genital warts and vulvar intraepithelial neoplasia among women with the human immunodeficiency virus.

Study design

This was a multicenter prospective cohort study comprised of women without warts or vulvar intraepithelial neoplasia at baseline who underwent CD4 count, human immunodeficiency virus RNA measurement, examination, Papanicolaou test, and biopsy, as indicated, every 6 months. Human papillomavirus DNA typing was examined at baseline.

Results

The incidence of warts among women who were human immunodeficiency virus seronegative was 1.31 versus 5.01 per 100 person-years among women who were seropositive (P<.001). Incidence of vulvar intraepithelial neoplasia among women who were seronegative was 1.31 versus 4.67 per 100 person-years among women who were seropositive (P<.001). In multivariable analysis, warts were associated with highly active antiretroviral therapy (relative hazard, 0.76), CD4 count (relative hazard, 0.91/100 cell/cm2 increase), acquired immunodeficiency syndrome (relative hazard, 1.25), abnormal Papanicolaou test results (relative hazard, 2.18), high- or medium-risk human papillomavirus types (relative hazard, 1.91), low-risk human papillomavirus types (relative hazard, 1.48), smoking (relative hazard, 1.43), having 1 child (relative hazard, 1.54), and age (relative hazard, 0.74/10 years). Vulvar intraepithelial neoplasia was linked to highly active antiretroviral therapy (relative hazard, 0.65), CD4 count (relative hazard, 0.92), abnormal Papanicolaou test results (relative hazard, 16.03), high- or medium-risk human papillomavirus types (relative hazard, 1.37), and age (relative hazard, 0.85/10 years).

Conclusion

Warts and vulvar intraepithelial neoplasia are common among women with human immunodeficiency virus. Highly active antiretroviral therapy decreases their incidence.

Section snippets

Methods

This investigation was part of the Women's Interagency HIV Study (WIHS), a multicenter prospective cohort study of the treated natural history of HIV infection and related health conditions among women who are HIV seropositive and at-risk HIV-uninfected women. The protocols, procedures, and baseline results of the WIHS have been described previously; WIHS participants are representative of US women with HIV.9 Briefly, in 1994 to 1955, 6 study sites enrolled 2628 women. After approval by local

Statistical methods

Tables were constructed that gave the total number of women in whom warts developed, the varying grades of intraepithelial neoplasia, and cancers. Incidence rates for the 3 outcomes were calculated as the number of incident events per person-years at risk. Exact 95% confidence intervals were determined on the basis of Poisson distributed counts.

To further investigate the incidence of each outcome over time, additional models were fit with the use of Poisson regression to investigate the

Results

After exclusions, 1562 HIV seropositive and 469 seronegative women were eligible for analysis. Table I shows the demographic features of the study population for each end point.

Genital warts

Incident warts were observed during follow-up in 382 women (24%) who were HIV seropositive and 35 women (7%) who were seronegative. The overall incidence of genital warts among seropositive women was 5.01 cases per 100 person-years (95% CI, 4.52, 5.53; P<.001 vs seronegative women) over 7631 person-years. Among seronegative women, the incidence rate for warts was 1.31 per 100 person years (95% CI, 0.92, 1.83) over 2664 person-years of observation. After up to 8 years of follow-up, the incidence

VIN

During the study, VIN of any grade was found in 359 women (23%) who were HIV seropositive and 35 women (7%) who were seronegative. Most VIN was low grade, and there was no significant difference in the distribution of disease by grade between seropositive and seronegative women (Table III). The incidence of any VIN among seronegative women was 1.31 per 100 person-years (95% CI, 0.91, 1.82) over 2678 person-years, although the overall incidence of VIN among seropositive women was 4.67 per 100

Vulvar cancer

No vulvar cancers were observed in women who were HIV seronegative. Three HIV seropositive women reported vulvar cancer during study. One woman had a verrucous carcinoma. Two patients had reports that showed stage IB squamous cell carcinoma of the vulva in association with VIN3. These 3 cases were observed during a total of 10,604 woman-years of observation, for an incidence rate of 2.21 per 10,000 woman-years (95% CI, 0.27, 7.97) among women who were HIV-seropositive.

Comment

Genital warts and VIN are common problems among women with HIV and are frequent reasons for referral to practicing gynecologists. Practitioners must understand how HIV infection modifies the natural history of genital warts and VIN to educate afflicted women and provide most appropriate treatment. We have shown that HAART reduces the incidence of genital warts and VIN 1. Although traditional ablative therapies remain appropriate, this finding may expand the indications for HAART to include

Acknowledgements

Data in this manuscript were collected by the WIHS Collaborative Study Group with centers (principal investigators) at the New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); the Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); the Los Angeles County/Southern California Consortium (Alexandra Levine); the Chicago Consortium (Mardge Cohen); and the Data Coordinating Center (Alvaro Munoz).

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☆

Supported in part by the National Institute of Allergy and Infectious Diseases, with supplemental funding from the National Cancer Institute, the National Institute of Child Health & Human Development, The National Institute on Drug Abuse, and the National Institute of Craniofacial and Dental Research. U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-HD-32632, U01-AI-34993, U01-AI-42590, M01-RR00079, M01-RR00083, and R01-CA85178-01.

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