Infection with anal human papillomavirus (HPV), a virus that can cause anal and cervical cancers, is associated with a higher risk of new HIV infection in previously HIV-negative men who have sex with men (MSM), according to new University of California, San Francisco, research.

RELATED ARTICLES
Study Examines Awareness of HPV
HPV Linked to Rise in Throat Cancer
Attacking From the Rear

Reported online ahead of print in the journal AIDS, the findings are available now. They are scheduled for publication in an upcoming print issue.

In previous studies, other sexually transmitted infections have been associated with higher risk of HIV infection. HPV is the most common sexually transmitted infection.

“We looked at HIV-negative men who have sex with men who were at high risk for HIV infection and who had multiple risk factors. Our results showed a strong independent association for increased risk of HIV acquisition among those men who were already infected with anal HPV,” said the study’s lead investigator, Peter V. Chin-Hong, MD, associate professor of clinical medicine at UCSF.

The 1,400 study participants were part of the EXPLORE trial, a large clinical trial to test the efficacy of a behavioral intervention for HIV-negative men who have sex with men with sites in Boston, Denver, New York City, and San Francisco. Risk factors were calculated from those men who became HIV-infected over the course of the trial, and infections were identified by blood tests.

“We think that HPV enhances susceptibility to HIV infection through two mechanisms,” said Chin-Hong. “Anatomically, the virus causes anal lesions. These lesions bring blood vessels closer to the surface, and also the lesions’ skin layer is thinner and more easily shredded, which frequently causes bleeding. These disruptions of the mucosal barrier could allow easier entry for HIV.”

In addition, HPV activates the immune system. The inflammatory cells recruited to the HPV lesions -- dendritic cells, macrophages, and CD4 T cells -- are the immune cells most susceptible to HIV infection.

HPV vaccine has been found effective in preventing acquisition of the virus by women. Clinical trials testing the effectiveness of the vaccine among men who have sex with men are currently under way.

“To date, the focus of attention on HPV has been almost exclusively on its key role in causing squamous cell cancer,” said the study’s senior investigator and author, Joel Palefsky, MD, professor of medicine and director of the Anal Neoplasia Clinic at UCSF. “This study points to another important means by which HPV infection may be associated with morbidity and mortality -- through potentiation of HIV infection. A direct role for HPV in this process will need to be confirmed in additional studies, and additional studies will be needed to understand the mechanisms by which HPV may do this.”

“But it is encouraging to note that to the degree that HPV truly plays a role in increasing the risk of acquiring HPV infection, primary prevention of HPV infection through HPV vaccination may potentially reduce that risk,” he added.

Coauthors of the study include Marla Husnik of the Fred Hutchinson Cancer Research Center in Seattle; Ross D. Cranston of the University of Pittsburg; Grant Colfax and Susan Buchbinder of the San Francisco Department of Public Health; Maria Da Costa and Teresa Darragh at UCSF; Dana Jones at the Centers for Disease Control and Prevention; Franklyn Judson of the Denver Department of Public Health; Beryl Koblin of the New York Blood Center; and Kenneth H. Mayer of the Fenway Community Health Center in Boston.