CROI 2011: HPV and Anal Cancer Research at CROI 2011

Human papillomavirus (HPV) infection remains common among people with HIV and anal cancer is still potentially deadly, researchers reported at CROI 2011.

Several abstracts covering various aspects of HPV in people with HIV were presented at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston. These studies highlight the continuing problem of this virus and its associated complications.

HPV can lead to anal cancer, which is among the most common non-AIDS-defining malignancies in HIV positive people; it can also cause cervical cancer, an AIDS-defining condition. Unfortunately cancer treatment remains invasive and toxic, and while vaccines recently approved to prevent HPV-related cancers are available, diagnosis and treatment remain critical research areas.

Anal Cancer Outcomes

Christian Hoffmann and colleagues (abstract 870) presented a poster describing clinical characteristics and outcomes of HIV positive patients with invasive anal cancer in a European cohort. The research team wanted to look at clinical outcomes with respect to antiretroviral use, specific cancer treatments, and other possible outcomes. They performed a retrospective analysis of all biopsy proven anal cancers in 92 patients.

The results showed a mean CD4 count of 351 cells/mm3 at the time of cancer diagnosis. A minority of the 92 participants had HIV RNA > 50 copies/mL. Mean duration of viral suppression was about 2.5 years. Most of the cohort was being treated with antiretroviral therapy (ART). After a mean follow-up period of over 2 years, anal cancer was the cause of mortality in 12 out of 19 deaths, which translated to 13% mortality from anal cancer.

The most important finding was that older age, CD4 cell count, and year of anal cancer diagnosis had no effect on survival. The researchers did find that the stage of cancer (III or IV, with IV being most severe) was associated with lower overall survival.

Types of anal cancer treatment varied among those who received surgery, but most used the chemotherapy agents mitomycin C and fluorouracil plus radiotherapy, or a combination of both. Those who received the combination had better survival rates compared to those who only received either chemotherapy or radiotherapy.

In this relatively small study it did not matter whether a patient had higher CD4 counts or was receiving ART as to the outcome of anal cancer. However, those who received a combination of chemotherapy and radiotherapy fared better, providing further evidence that this is the preferred treatment approach.

HPV Prevalence

A French study by Christophe Piketty and colleagues (abstract 871) dug a bit deeper in regard to antiretroviral treatment and HPV seroprevalence among gay men. In a longitudinal cohort of 94 men who have sex with men (MSM), the researchers tracked initiation of ART and anal cell abnormalities.

A total of 76 participants had at least 2 visits with available anal cytology results. Of these, 56 participants had HPV 16, the subtype most often associated with anal cancer. The median age was 39.4 years and the baseline median CD4 count and viral load were 301 cells/mm3 and 4.9 log copies, respectively. After 2 years follow-up the median CD4 count rose to 545 cells/mm3 and HIV levels were undetectable in 96% of participants.

A strikingly high 90% of participants had high-risk HPV anal infection at baseline, whereas 87% did so at the end of the study. The follow-up analysis looked at prevalence of 3 higher-risk HPV subtypes -- 16, 18, and 45 -- at various time points (baseline, 12, and 24 months).

The reported data indicate stable HPV infection with higher-risk subtypes that may predispose gay men to develop anal cancer over time, despite effective antiretroviral therapy. However, the study did not report anal cancer cases in this 2-year time period.

HPV Vaccines

Two HPV vaccines are currently approved for women in the U.S. Recently young men were added to the indication, though vaccination for men is not recommended by the Centers for Disease Control and Prevention (CDC). The Gardasil vaccine protects against 4 HPV subtypes known to cause anal and cervical cancer (16, 8, 6, and 11) and Cervarix protects against subtypes 16 and 18.

While the current vaccines appear to be highly protective against HPV infection for people uninfected with the higher-risk subtypes, they might also be beneficial for those who may not yet have acquired every high-risk strain.

Several studies at CROI demonstrated this possibility by looking at subtype prevalence. Investigators with ACTG A5240 (abstract 762) analyzed HPV subtypes in over 292 HIV positive women in 2 groups, those with > 350 CD4 cells/mm3 and those with between 201 and 350 cells/mm3.

In both groups overall HPV prevalence was lower than expected based on what has been previously reported for each subtype. This led the researchers to conclude that it may be feasible to effectively vaccinate those women who had not been exposed to all the high-risk subtypes. A second international study (abstract 763) of HIV positive women produced similar findings.

In the French study mentioned above, gay men also had lower prevalence of the higher risk HPV subtypes, leaving the potential for protective vaccination. However, insurers will most likely not reimburse the vaccine for HIV positive gay men over 26 years old, since the vaccine is not recommended by the CDC.

Additional studies need to be performed to determine whether vaccines will work in people who have already had sexual exposure to HPV, and if vaccination will prevent anal and cervical cancers in people with HIV. Until these studies are completed, however, some experts are urging the CDC to revise its recommendation now in order to prevent cancer in gay men currently living with HPV who might still be protected from other types.

Investigator affiliations:

Abstract 870: ICH, Hamburg, Germany; IFI Inst Hamburg, Germany; Univ of Cologne, Germany; Praxis Driesener St, Berlin, Germany; Univ of Bonn, Germany; Ludwig-Maximilians-Univ, Munich, Germany; MVZ Karlsplatz, Munich, Germany; Private Practice, Berlin, Germany; Univ of Essen, Germany.
Abstract 871: Hosp European Georges Pompidou, Paris, France; INSERM U943 and UMR S943, Univ Pierre and Marie Curie, Paris, France; Hosp Pitie-Salpietrierre, Paris, France; Univ Paris 5 France, Hosp Necker, Paris, France; Hosp St. Antoine, Paris, France.

Abstract 762: The Miriam Hosp, Brown Univ, Providence, RI; New York Univ School of Medicine, New Work, NY; Harvard School of Public Health, Boston, MA; ACTG Operations Ctr, Silver Spring, MD; NIAID, NIH, Bethesda, MD.

Abstract 763: Univ of the Witwaterstrand, Johannesburg, South Africa; Clinical Research Inst Evandro Chagas, Rio de Janeiro, Brazil; Univ of Botswana, Gaborone, Botswana; Vanderbilt Univ, Nashville, TN; Harvard Univ, Boston, MA.

4/1/11

References

C Hoffmann, M Sabranski, C Wyen, et al. Clinical Characteristics and Outcome of HIV+ Patients with Invasive Anal Cancer. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 870.

C Piketty, A Si-Mohamed, E Lanoy, et al. 24 Months of cART Is Not Associated with a Reduction of Anal HPV Infection in HIV+ MSM. Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 871.

E Kojic, M Cespedes, T Umbleja, et al. Baseline Seroprevalence of HPV Vaccine Types 6, 11, 16, and 18 in HIV+ Women Receiving the Quadrivalent Vaccine in the AIDS Clinical Trials Group Study A5240. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 762.

C Firnhaber, D Evans, R Khalili-Friedman, et al. Seroprevalence of HPV Vaccine Types 6, 11, 16 and 18 in HIV+ Women from South Africa, Brazil, and Botswana. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 763.