HIV-positive women who do not have cervical infection with human papilloma virus and a good immune system do not have a greater risk of developing precancerous cervical lesions than HIV-negative women, according to a US study published in the March 23rd edition of the Journal of the American Medical Association. However, the investigators found a high incidence of precancerous lesions in HIV-positive women with CD4 cell counts below 500 cells/mm3 even if they were infected with a strain of human papilloma virus not considered high risk for cervical cancer. The investigators suggest that further studies should be conducted to determine if HIV-positive women should be tested for HPV.
Guidelines for cervical screening of HIV-positive women have not been updated in the US since 1995. They state that an HIV-positive women should have two PAP smears six months apart immediately after HIV diagnosis, and if the results are normal, annual screens thereafter. The guidelines do not recommend testing for HPV, even though economic models suggest that this would be highly cost effective. In the UK, a cervical screen is recommended for all women at the time of their HIV diagnosis followed by further annual screens if normal.
Accordingly, investigators from the ongoing US Women’s Interagency HIV Study (WIHS) sought to determine if a single baseline HPV test can be used to determine the appropriate frequency of cervical screening for HIV-positive women with normal baseline cytology.
A total of 855 HIV-positive women with a mean age of 36 years, and 343 HIV-negative women with a mean age of 34 years were included in the investigators’ analysis. At baseline, and then at six monthly intervals all the women underwent a pelvic examination with cervicovaginal lavage collected for HPV testing, followed by a PAP smear. HIV-positive women also had blood samples obtained which were used to measure CD4 cell count.
Investigators then calculated the cumulative incidence of any squamous intraepithelial lesions (precancerous lesions), high grade squamous intraepithelial lesions, and cervical cancer according to baseline HPV results and stratified these according to HIV status and CD4 cell count. Data were collected for seven years, but censored after five.
At baseline, significantly more HIV-positive women had HPV (52% versus 27%, p < 0.001), types of HPV associated with the later development of cancer (19% versus 5%, p < 0.001), and non-cancer causing HPV (33% versus 22%, p < 0.001).
After two years of follow-up, 9% of women with a CD4 cell count below 200 cells/mm3, 9% of women with a CD4 cell count between 200 – 500 cells/mm3, and 4% of women with a CD4 cell count above 500 cells/mm3 had developed precancerous lesions. However, there was no large or significant absolute difference in the incidence of precancerous lesions between the HIV-negative women (3%) and the HIV-positive women.
This was no longer the case after three years of follow-up. Women with a CD4 cell count less than 200 cells/mm3 and between 200 – 500 cells/mm3 had a cumulative incidence of precancerous lesions of 29% and 14% respectively, compared to only 6% for HIV-positive women with a CD4 cell count above 500 cells/mm3 and 5% for HIV-negative women.
Precancerous lesions occurred most frequently after two years in women with types of HPV not associated with a high risk of cervical cancer. In total 31% of individuals with a CD4 cell count below 200 cells/mm3, and 24% of women with a CD4 cell count between 200 – 300 cells/mm3 had squamous intraepithelial lesions, compared to only 6% of HIV-positive women with a CD4 cell count above 500 cells/mm3 and 8% of HIV-negative women. There were no cases of high grade precancerous lesions or cervical cancer in either HIV-positive or HIV-negative women during the follow-up period.
Of the HIV-positive women with types of HPV considered high risk for cervical cancer, 21% with a CD4 cell count below 200 cells/mm3 and 15% with a CD4 cell count between 200 – 500 cells/mm3 had developed precancerous lesions after two years. This compared to only 5% of HIV-positive women with a CD4 cell count above 500 cells/mm3 and 4% of HIV-negative women. There were three cases of high grade precancerous lesions in HIV-positive women, two in individuals with a CD4 cell count above 500 cells/mm3.
Even after three years the cumulative total of precancerous lesions was comparable for HIV-positive women with a CD4 cell count above 500 cells/mm3 (9%) and HIV-negative women.
Using multivariate Cox models, which controlled for race and age, the investigators confirmed that the incidence of any precancerous lesions was similar for HIV-negative women and HIV-positive women with a CD4 cell count above 500 cells/mm3 who were negative for high risk HPV (hazard ratio: 1.2) and negative for all HPV (hazard ratio: 1.4). HIV-positive women with a CD4 cell count below 500 cells/mm3 had a greater of risk of precancerous lesions after just two years than HIV-negative women, even if negative for any HPV (hazard ratio 2.9).
“In this observational cohort study, HIV seronegative and HIV seropositive women who had normal cytology results with CD4 cell counts greater than 500 cells/mm3 and who had negative results for HPV at baseline had a similar low cumulative incidence of any SIL for three years or more”, write the investigators.
Given the observational nature of their study the investigators note that their findings should be treated with some caution. They also warn that testing, and notifying a woman of HPV infection can have "psychosocial costs", but conclude “the use of HPV testing in HIV-seropositive women warrants evaluation in a formal clinical trial.”
Reference
Harris TG et al. Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus results. JAMA 292 (12): 1471 – 1476, 2005.