European AIDS Clinical Society strengthens HPV vaccination advice

New European guidance responds to growing evidence of anal cancer risk in HIV-positive men who have sex with men

The European AIDS Clinical Society (EACS) has recommended HPV (human papillomavirus) vaccination for everyone living with HIV aged under 26 and all men who have sex with men up to the age of 40.

HPV is a sexually transmitted virus that causes genital warts, and in some forms, leads to the development of cervical, anal and oropharyngeal cancers. Anal cancer, rare in the general population, is becoming more common in people living with HIV, especially men who have sex with men.

HPV vaccination

Deborah Konopnicki of St Pierre University Hospital, Brussels presented a review of the evidence supporting vaccination against HPV in people living with HIV at last month’s 16th European AIDS Conference (EACS 2017) in Milan.

Screening for HPV-related cancers is inconsistent and for anal cancer, the choice of screening technique is still a matter of debate, she said. As for oropharyngeal cancers caused by HPV, whether to screen for these conditions is still unclear.

Glossary

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

morbidity

Illness.

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

cervix

The cervix is the neck of the womb, at the top of the vagina. This tight ‘collar’ of tissue closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

Greater use of preventive vaccines has the potential to reduce HPV-associated morbidity. Vaccination of girls and young women has resulted in significant reductions in HPV-associated morbidity in Australia, Denmark and Scotland, within ten years of the first vaccination programmes.

Only one study, the ACTG 5298 study, has looked at the effect of vaccination on protection against HPV infection in HIV-positive adults. That study found that in a predominantly male population with a median age of 47 years vaccination did not reduce persistent infection with HPV.

This finding led EACS to recommend that HPV vaccination should be offered to people with HIV aged 26 and under. EACS has also followed the British HIV Association in recommending vaccination for all men who have sex with men with HIV under the age of 40. Previous guidance issued in 2015 recommended that doctors should follow national guidance on HPV vaccination.

Although EACS states that the efficacy of the vaccine is questionable in people who have already been exposed to HPV, Deborah Konopnicki said it is still plausible that vaccination could improve protection against HPV-associated disease.

The ACTG A5240 study showed that in women already seropositive for any of the HPV types included in the quadrivalent vaccine, vaccination resulted in a substantial increase in HPV antibody titres (levels) (+1.5 log10 IU/ml).

There is also some evidence from studies in HIV-negative women and men who have sex with men that vaccination after the treatment of HPV-associated cervical or anal lesions is associated with reductions in recurrence of lesions. Two ongoing studies are likely to provide further information on vaccination’s role in the prevention of recurrence in people living with HIV.

Vaccination results in greater antibody responses in women living with HIV who already have undetectable HIV viral load at the time of the first vaccination, probably because viral suppression permits immune restoration.

EACS recommends the 9-valent HPV vaccine if available (active against nine common types of HPV). Dr Konopnicki noted that there is no evidence in people living with HIV to support anything less than a 3-dose vaccination schedule, although several studies in young women have shown that a single vaccination is just as immunogenic as multiple vaccinations.

Anal cancer

Research from Austria presented at the conference by Robert Zangerle of the Medical University, Innsbruck, showed that by 2015, anal cancer had already affected at least one in forty men who have sex with men receiving care in clinics affiliated to the Austrian HIV Cohort Study. Dr Zangerle said that the rate was already “alarmingly high”.

The cohort covers around three-quarters of people receiving HIV care in Austria (7511 people). Between 2003 and 2015, 46 cases of anal cancer were diagnosed, 63% in men who have sex with men. The overall incidence was 52.5 cases per 100,000 person-years of follow-up but was higher in men who have sex with men (95.1 per 100,000 person-years) and lower in women (36.5 per 100,000 person-years).

By 2015, 0.8% of men who have sex with men in care who were under the age of 50 had ever been diagnosed with anal cancer, but the cumulative prevalence rose to 2.6% in men who have sex with men over the age of 50 and 1.6% in women with HIV aged 50 and over. In summary, the Austrian cohort study found that one in forty men who have sex with men with HIV aged 50 and over had already been diagnosed with anal cancer, and the median age of the over-50 age group was 56 years, suggesting that anal cancer could continue to be a significant cause of disease as men age.

References

Konopnicki D et al. HPV vaccination: who to vaccinate, which vaccine to use, how to evaluate the success of vaccination. 16th European AIDS Conference, 25-27 October, Milan, mini-lecture 3, 2017.

Zangerle R et al. The incidence rate of anal cancer in the Austrian HIV Cohort Study. 16th European AIDS Conference, 25-27 October, Milan, abstract PS7/2, 2017.