HIV-positive teenage girls are already infected with many of the human papillomavirus (HPV) subtypes that are considered high risk for cervical cancer, and the infection persists almost twice as long as in HIV-negative teenagers, according to the results of a US study published in the July 1st issue of The Journal of Infectious Diseases. This places the girls at a higher risk of developing cervical cancer in adulthood, and more frequent screening, as well as vaccine trials aimed at HPV prevention, should take place, argue the study's authors.
The Reaching for Excellence in Adolescent Care and Health (REACH) project of the Adolescent Medicine HIV/AIDS Research Network includes HIV-positive teenagers from 13 US cities, aged 13-18, as well as HIV-negative teenagers considered at high risk of acquiring HIV. This study focused on the 411 girls in the REACH master data file as of March 2001. Of these 411 teenage girls, 334 (222 HIV-positive and 112 HIV-negative) met the criteria for this study, which was to have pre-existing or new HPV infection during the course of the study.
For the purposes of this study, the researchers divided the myriad HPV subtypes into those associated with a low and a high risk of cancer. Low-risk subtypes included 6, 11, 42, 44, 54, 40, 13, 32, 62, 72, 2, 57, and 55. High-risk subtypes were defined as 16-like (16, 31, 33, 35, 52, 58, and 67), 18-like (18, 39, 45, 59, 68, 70, 26, 69, and 51), and 56-like (56, 53, and 66).
Although rates of new infections were similar between the two groups, the HIV-positive teenage girls were more likely to be already infected with multiple high-risk subtypes compared with the HIV-negative girls (40.7% vs. 22%, respectively; p = .0026). This corresponds with the study’s finding that the HIV-positive teenagers had been exposed to more HPV since they had experienced higher-risk sexual behaviour, were younger when they began to have sex, and had a greater number of partners during their lifetime than the HIV-negative teenagers.
When the researchers analysed the time to clearance of the pre-existing HPV subtypes seen in the girls at the start of the study, 59% of the HIV-positive teenagers versus 75.9% of the HIV-negative teenagers had HPV clearance of all initial HPV subtypes by the end of the study. It also took longer for the HIV-positive teenagers than the HIV-negative teenagers to clear the HPV (a mean of 689 days vs. 403 days, respectively).
A similar pattern was observed when it came to the clearance of the high-risk HPV subtypes, taking almost twice as long for the HIV-positive teenagers to clear the high-risk subtypes compared with the HIV-negative teenagers. For example, for those who cleared the virus, it took an average 849 days for the HIV-positive teenagers to clear subtype 16-like HPV, compared with 468 days for the HIV-negative teenagers.
When it came to identifying which factors affected the loss of high-risk HPV subtypes over time, multivariate analysis found several factors statistically significant.
The HIV-negative teenagers were found to be about 40% more likely to clear the high-risk subtypes than the HIV-positive teenagers (hazard ratio [HR], 1.38 [95% CI, 0.99-1.93]; p =.061). Interestingly, the use of marijuana was also positively associated with HPV clearance (HR, 1.51 [95% CI 1.12-2.03], p=.007). The authors theorise that this association could be due to the fact that marijuana use increases natural killer cell activity, which was not examined in this study “but may be an interesting focus for future studies.”
It appears that the role of HIV infection in the persistence of HPV subtypes is a complex issue. For every 100 cell/mm3 rise in absolute CD4 cell count, there was a six percent increase in the likelihood of HPV clearance (p=.015). “The lower the CD4 count, the more likely that HPV infection will persist,” wrote the study’s authors.
However, they also found that regardless of CD4 count, the presence of multiple HPV subtypes was also a factor; infection with just one group of low- or high-risk subtypes was associated with a halving of HPV persistence compared to infection with two or more groups of subtypes, independent of CD4 count. “This,” they suggest, “may reflect a dysfunction in the immune system that is not indicated by CD4 cell counts.” One theory is that there is a re-emergence of latent HPV subtypes in HIV-positive women; another is that the different subtypes of HPV infection affect each other interdependently, which aids their survival.
The study’s authors conclude that HIV-infected teenage girls are “at risk for persistence of high-risk HPV types” and that this “underscores the importance of prevention of HPV infection. Vaccine trials for prevention of HPV infection should be targeted for HIV-infected adolescents.”
Further information on this website
Genital Warts - factsheet
HIV & Women - booklet in the Information series for HIV-positive people (pdf)
HPV infection more common in HIV-positive women who smoke - news story
Invasive cervical cancer risk no higher in women with HIV - news story
Moscicki AB et al. Persistence of human papillomavirus infection in HIV-infected and –uninfected adolescent girls: risk factors and differences, by phylogenic type. J Inf Dis 190, 37-45, 2004.