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HPV Likely but Etiology Uncertain in HIV Positive : Coinfection often includes a higher prevalence of high-risk strains; is it persistence or reinfection?


 

MIAMI BEACH — Human papillomavirus is often present in women who are HIV positive, but it remains unknown whether affected women are experiencing HPV reactivations, reinfections, or both, Dr. Matthew Pearson said at an ob.gyn. conference sponsored by the University of Miami.

Clinicians who treat women infected with HIV also are likely to see human papillomavirus (HPV) infection, including a higher prevalence of high-risk strains, compared with the general population.

Progression and persistence of HPV are associated with poorer HIV infection status, indicated by either low CD4 counts and/or high viral loads in most studies.

An estimated 50 million people are infected with HIV worldwide, including more than 1 million in the United States, according to the Centers for Disease Control and Prevention.

Also, there are an estimated 256 million people infected with HPV worldwide. In 1993, the CDC defined cervical cancer as an AIDS-defining illness.

“So is this a function of persistence or reinfection? Does the HPV go away and then the person gets reinfected?” asked Dr. Pearson, of the division of gynecologic oncology, University of Miami.

To try to answer this question, researchers looked at the natural history of coinfection in 2,362 women at a mean follow-up of 3 years (J. Natl. Cancer Inst. 2005;97:577–86).

The participants included 1,848 HIV-positive and 514 HIV-negative women enrolled in the longitudinal Women's Interagency HIV Study in 1994 or 1995 (http://statepiaps.jhsph.edu/wihs

They found the rate of HPV clearance was lower among HIV-positive women (hazard ratio, 0.67), which suggested that persistence is a factor. However, the researchers also found that condom use decreased new HPV infections in women who had three or more partners.

“This is consistent with the idea of reinfection from new partners,” Dr. Pearson said.

In 2001 and 2002, investigators for the Women's Interagency HIV Study enrolled an additional 1,144 women to assess the impact of highly active antiretroviral therapy (HAART). These additional participants included 406 HIV-negative women, 254 HIV-positive and HAART-naive women, and 484 HIV-positive HAART-treated women.

An estimated 13% of women treated with HAART had regression of their cervical squamous intraepithelial lesions each year, compared with no regression in the non-HAART group (J. Natl. Cancer Inst. 2004;96:1070–6). After a median of 2.7 years, 45% had lesions that regressed to normal cytology in the HAART group, compared with 59% in HIV-negative women.

There is no consensus about whether routine testing for HPV should be done to screen for abnormalities, Dr. Pearson said. However, HPV screening can guide the frequency of subsequent cancer screening.

For example, when a new HIV-positive patient presents and HAART is prescribed, monitor the patient with a Pap test and HPV DNA analysis at 6 months and 1 year, Dr. Pearson suggested.

If the Pap test results are negative and no high-risk HPV strain is detected, schedule an annual Pap/HPV test. If the patient is Pap negative but HPV positive for high-risk strains, schedule for a follow-up Pap test every 6 months.

If no HAART is prescribed and the CD4 count is greater than 500 cells per microliter, monitor the patient with a Pap test and HPV DNA analysis at 6 months and 1 year, Dr. Pearson suggested. However, if the patient has a CD4 count of 500 cells per microliter or below, schedule a follow-up Pap test every 6 months.

Each HPV type in the quadrivalent vaccine (Gardasil, Merck) is more prevalent among HIV-positive women than in the general population (J. Natl. Cancer Inst. 1999;91:226–36). These researchers concluded that prevalence of oncogenic HPV strains increases as CD4 counts decrease. Also, they found HIV-positive participants are more likely to be infected with multiple HPV strains; 23% of HIV-positive participants had two or more HPV types present.

Multiple HPV types also were more prevalent in HIV-positive women than in the general population (41% vs. 7%, odds ratio 9.3) in a meta-analysis of 20 studies with a total of 5,578 women (AIDS 2006;20:2337–44).

These researchers also found multiple HPV types increasingly often as grade or abnormality on the Pap test increased. And, Dr. Pearson noted, “HPV 16 nearly tripled from low-grade to high-grade Pap smears.”

“The question still remains if we should be vaccinating immunocompromised or HIV-positive women,” Dr. Pearson said. “The CDC thinks it is worthwhile.” Regarding the HPV vaccine, the CDC stated: “Immunocompromised females, either from disease or medication, can receive this vaccine; however, the immune response to vaccination and vaccine efficacy might be less than in immunocompetent females.”

This view is shared by the Society of Gynecologic Oncology in their Statement on the Cervical Cancer Vaccine and the American College of Obstetricians and Gynecologists in their Committee Opinion #344, Dr. Pearson added.

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