BETHESDA, MD. — HIV-infected women shed more human papilloma virus, have higher rates of high-grade cervical intraepithelial neoplasia, and are diagnosed more frequently with vulvar intraepithelial neoplasia (VIN) than are women who are not infected, Thomas C. Wright Jr., M.D., said at a conference on vulvovaginal diseases.
Women infected with HIV have an increased rate of human papilloma virus (HPV) shedding that is generally estimated at about four times that of HIV-negative women, said Dr. Wright, director of obstetrics, gynecology, and pathology at Columbia University College of Physicians and Surgeons, New York.
Among HPV-infected women, those who are also infected with HIV have more HPV types than do women without HIV. In one study conducted in New York City, 31% of HIV-positive women had more than one HPV type, vs. 9% of HIV-negative women. A total of 16% and 14% had HPV 16 and HPV 18, respectively, in the HIV-positive group vs. 6% and 3%, respectively, in HIV-negative women.
Studies conducted in the 1990s determined that the distribution of HPV types in women without cervical intraepithelial neoplasia (CIN) tend to be the same in those who are HIV positive and those who are HIV negative. But women with biopsy-confirmed CIN 2,3 who are HIV positive “tend to be more heterogenous for high-risk [HPV] types” he said.
Types 16 and 18, which tend to be the most common high-risk HPV types in the general population and appear to be more aggressive than other high-risk HPV types, are found in considerable numbers of CIN 2,3 cases in both HIV-infected and uninfected women. However, in HIV-infected women, the other HPV types that can cause cancer “may become a little more pathogenic” as the immune system deteriorates, Dr. Wright noted.
Viral load and CD4 counts have both been found to be markers for patients who shed HPV: The Women's Interagency HIV Study (WIHS) published in 1999 found that HPV was detected more frequently in women with low (under 200) CD4 counts, regardless of their HIV viral load. Similarly, women with a high HIV viral load, even with a higher CD4 count, will have high rates of HPV shedding, Dr. Wright said at the conference, sponsored by the American Society for Colposcopy and Cervical Pathology.
For more than a decade, it has been clear that the prevalence of CIN among HIV-positive women is high, estimated at two to four times higher than among noninfected women. He referred to four large prospective follow-up studies, including one he and his associates conducted in New York City, which found that the rates of abnormal cytology in HIV-positive women ranged from 30% to 40%, vs. 8% to 20% among HIV-negative women.
In his study, 7% of the HIV-positive women had high-grade CIN (CIN 2,3), vs. 1% of the HIV-negative women. Over a 3-year follow-up, 20% of the HIV-positive women developed biopsy-confirmed CIN, increasing to 30% over 6 years. Predictably, a woman with low CD4 counts is more likely to develop CIN, Dr. Wright said, adding that a woman with low CD4 counts who is followed for 48 months has a 40% chance of developing biopsy-confirmed CIN.
In HIV-infected women condylomas are very common. Vulvar condylomas in this population are numerous and multifocal, and tend to respond poorly to standard treatments, he said. Although VIN is less common than is CIN, VIN is much more common in HIV-infected women compared with uninfected women.
In a study published this year of 1,778 HIV-infected women and 500 HIV-negative women followed for 8 years, incident condylomas were detected in 23% of HIV-positive women vs. 7% of HIV-negative women. In the WIHS study published this year, risk factors for condylomas identified among HIV-positive women were cytologic abnormalities, HPV, smoking, no HAART (highly active antiretroviral therapy), and a low CD4 count, he said.
Now that HAART is used so widely, there is much less cervical and vulvar disease in HIV-infected patients, Dr. Wright observed. At one point, a large proportion of the patients he saw at the Columbia colposcopy clinic were HIV positive, but those numbers have markedly dropped now that most are on HAART, which has been shown to reduce the incidence of condylomas.
VIN, however, is clearly an increasing problem in this population, he said. Because women in the HIV clinic are well screened and treated with loop electrosurgical excision procedure when CIN is detected, cervical cancer is less common. In contrast, “we continue to identify vulvar cancers,” since screening and treating for VIN lesions is not as thorough.
In a study that followed cervical disease in HIV-positive and HIV-negative women, he and his coinvestigators have found that about 4% of HIV-positive women developed biopsy-confirmed VIN over 60 months vs. less than 1% of HIV-negative women. And, as with cervical disease, the risk was higher with lower CD4 counts, where almost 20% of those with CD4 counts under 200 developed biopsy-confirmed VIN.