A high prevalence of oncogenic human papillomavirus (HPV) was found in women living with HIV, and the prevalence was highest in the anal canal, according to a multicenter French study.
The study, presented at ICAAC 2014 by Isabelle Heard, M.D., joint-director of the French National HPV Laboratory, Institute Pasteur, found that the prevalence of HPV16 -- the most oncogenic genotype of HPV -- was three-times higher in the anus than in the cervix.
Notably, the participants did not report risk behaviors that would lead to transmission to the anal canal of HPV. Rather, the study found that high risk HPV was prevalent in those with lower CD4 counts (below 350) and with a history of having had a cervical lesion -- suggesting that, in more immune-compromised women, the infection may spread from the cervix to become more persistent in the anus.
Persistent infection with a high-risk oncogenic genotype of HPV (HR-HPV) in the anus and in the cervix can lead to invasive squamous cell carcinoma, according to previous research, and an increasing body of data shows that coinfection with HIV increases the risk for cancer at each site.
Recent reports have found women living with HIV to have incidence rates of anal cancer that are 14 times higher than in the general population. However, relatively little is known about anal HPV infection or the natural history of anal HPV infection in the context of women living with HIV. Heard also pointed out that, at the moment, there is no consensus on optimal screening for both cervical and anal cancer in women living with HIV.
Heard and her colleagues designed a sub-study nested in the ANRS CO17 VIHGY cohort (a prospective cohort study looking primarily at cervical HPV in women living with HIV) to determine the overall and type-specific HPV prevalence in the anal canal and cervix. The sub-study also sought to compare the characteristics of HR-HPV infection in each site and to describe risk factors for the infection at each site.
During gynecological visits in 2012, the women living with HIV in the cohort were asked if they would be willing to participate in a two-step study, which involved an anal HPV screening test -- apart from during the gynecological visit -- and for those who accepted, a high resolution anoscopy.
The HPV screening and testing involved collecting anal specimens during a gynecological visit prior to collection of the specimens for cervical testing. The specimens were screened for what have been defined as high-risk genotypes of HPV: 16, 18, 31, 33, 58, 35, 39, 45, 51, 52, 56, 59 and 68.
About 91% of the women agreed to participate. The median age of participants was 45, about 85% were on effective antiretroviral therapy with an undetectable viral load, and the median CD4 count was 612. Notably, 50.5% had prior cervical lesions (including both low- and high-grade), and 25.1% had already undergone surgery due to high-grade cervical lesions.
Results: Anal and Cervical HPV Infection
HR-HPV infection and HPV16 infection -- the genotype responsible for at least 50% of cervical cancer -- were significantly more prevalent in the anal canal compared to the cervix.
- HR-HPV was found in 55% of the anal specimens, and 33% of the cervical specimens (P < .0001).
- HPV-16 was found in 13% of the anal specimens and 5% of the cervical specimens (P = .0002).
- Multiple infections (with more than one HPV genotype) were also more frequently observed in the anal canal (80.5%) than in the cervix (66.3%) (P < .0001).
- HPV16 was the most prevalent genotype in the anus as well as in the cervix.
- Each genotype was more prevalent in the anus as compared to the cervix.
- HPV16 and HPV18 together were detected in 19% of the anal samples and 5% of the cervical samples.
- 35.4% of the participants did not have any infections with oncogenic genotype [in] the anal canal or in the cervix.
- 31.2% had only anal HR-HPV infections.
- 23.5% had HR-HPV in both sites infected.
- 9.9% had only cervical HR-HPV infection.
Risk Factors for Prevalent Anal HR-HPV
The study found a number of risk factors associated with having HR-HPV in the anal canal, including being aged 4049, having a CD4 count below 350, a history of cervical lesions, and the presence of oncogenic genotype in the cervix other than HPV16.
"We did not find that having a history of anal sex or having HR-HPV 16 in the cervix was a risk factor for anal HR-HPV infection," Heard said.
Risk Factors for Prevalent Cervical HR-HPV
The risk factors associated with having HR-HPV in the cervix included geographical origin (women with HR-HPV were more likely to come from sub-Saharan Africa), nadir CD4 count below 350, history of cervical lesions, and the presence of any HR-HPV in the anal canal.
Why the higher prevalence in the anal canal? "It is possible that the longer persistence of low-grade lesions in the cervix that is not treated because there is no reason to treat them, allows HR-HPV transmission to the anal canal," said Heard.
However, these findings provide cause for concern. In the absence of screening for HPV in the anal canal -- which is the case at the moment -- persistent infection opens the door for future anal disease and cancer in HIV-positive women who are living longer due to the efficacy of antiretroviral treatment.
"We may suggest that anal cancer screening could be offered to all HIV-infected women, and at least to those with a history of cervical lesions during their gynecological examination," concluded Heard.
Theo Smart is an HIV activist and medical writer with more than 20 years of experience.