HIV-positive women often infected with multiple high-risk HPV strains not covered by vaccine

HIV-positive women often have cervical infection with multiple strains of human papilloma virus (HPV) which are associated with cancerous and precancerous changes to the cervix, according to a US study published in the August 15^th edition of the Journal of Infectious Diseases. Although HPV genotypes 16 and 18 are most frequently associated with an increased risk of cervical cancer in both HIV-positive and HIV-negative women, the US researchers found that women in their study were often infected with multiple genotypes of HPV and that strains of the virus other than 16 and 18 were associated with a high risk of pre-cancerous and cancerous cell changes. The investigators suggest that this finding has implications for HPV vaccine research that has focused on genotypes 16 and 18.

HIV-positive women have a higher rate of cervical infection with HPV as well as elevated rates of pre-cancerous and cancerous cell changes in the cervix than do HIV-negative women. There is, however, limited information about the prevalence of specific HPV types amongst HIV-positive women in the US, so between 1996 and 2003, investigators at the University of Rochester undertook a seven year prospective study, involving 229 women receiving routine HIV care. Cervical lavage samples were obtained to check for the presence of HPV and to determine their type and Pap smears were conducted to see if the women had any abnormal cell changes in the cervix.

The women has a median age of 35 years, 88% had been infected with HIV through sex, and 10% by injecting drug use. Median CD4 cell count was 372 cells/mm³ and median viral load was a little under 3,000 copies/ml.

A total of 202 women provided samples suitable for HPV genotyping. Samples provided by 105 women were positive for HPV. Of these samples, 52% were positive for multiple types of HPV. The most commonly detected type of HPV was HPV-56 (27%), followed by HPV-53 (18%), HPV-16 (12%), HPV-58 (10). In addition HPV-33, HPV-52, HPV-MM7 and HPV-MM8, and were each found in 9% of samples.

During the seven years of the study, 709 Pap smear samples were obtained and 32% of these showed some abnormality. Just under a half of these abnormal samples were of undetermined significance, but 37% showed low-grade pre-cancerous cell changes in the cervix and 6% high-grade pre-cancerous cell changes.

The investigators then looked to see if any particular HPV genotypes were associated with cell changes and established that genotypes HPV-58, HPV-56, HPV-53, HPV-52, HPV-33 and HPV-18, HPV-16, HPV-MM7 and MM-8 were all associated with cell abnormalities.

After controlling for factors including CD4 cell count, viral load, number of sexual partners and smoking, the investigators found that women infected with HPV-16 and HPV-18 were 23 times more likely to have abnormal cervical cells than women who were not infected with HPV. In addition, women infected with other high-risk HPV genotypes were six times more likely than women who were not infected with HPV to have abnormal cervical cells.

An association was also found between HIV viral load and the risk of having abnormal cervical cells. For each log₁₀ increase in HIV viral load, the risk of having abnormal cervical cells increased 1.6 compared to women whose viral load did not increase.

HPV-16 and HPV-18 are most frequently associated with abnormal cell changes in both HIV-positive and HIV-negative women. It has been theorised that HPV-16 is better adapted to evade the immune system, therefore ensuring that it is found at higher prevalence amongst women with well preserved immune function. However, amongst women with lower CD4 cell counts, other HPV types may, the investigators suggest, be able to cause cell changes.

This finding could have implications for HPV vaccine research, which currently focuses on HPV-16 and HPV-18. “To prevent the majority of cervical infection and disease in HIV-infected populations may require that vaccine preparations contain additional types”, comment the investigators.