Vaccinate against Anal Cancer?

posted: 27/07/2009

Anal cancer in men with HIV is much more common now since modern treatments became standard, but could HPV vaccination help prevent this?
 

HPV basics

Human papilloma viruses are known as HPV. They can affect the skin and the moist membranes that line parts of the body, including

• the lining of the mouth and throat 
• a woman's cervix
• the anus.

There are more than 100 different types (or ‘strains’) of human papilloma virus (HPV). Each type has a different number.

HPV is common. Most people have the virus at some time in their lives. For most people it causes no symptoms and goes away on its own.

Some types of HPV can cause precancerous changes in the cells of the anus, cervix or the lining of the mouth and throat. They are known as high risk HPVs. The changed cells have a bigger risk of becoming cancerous than normal cells.

Last week we reported how HPV raises the risk of cancer of the cervix to women living with HIV. Now we look at anal cancer, which is caused by the same virus.

The annual incidence of anal cancer amongst people with HIV has continued to increase in recent years and now stands at 128 cases per 100,000 or one case in 784 people, the Fifth IAS Conference was told. This is nearly 100 times the rate in the general population (1.4 per 100,000).

9 out of 10 HIV+ men might get some benefit from HPV vaccination

The USA's Veterans Administration Healthcare System told the conference that a study of HIV/HPV co-infected army veterans implied that up to 89% of men with HIV could potentially derive at least some benefit from one of the currently-licensed HPV vaccines, and 53% of men would get substantial benefit.

Could HPV vaccine help?

In a study of patients who were once in the USA armed forces, Dr Stephen Berman investigated infection with human papilloma virus (HPV) and its subtypes in 62 HIV-positive men, 90% of them gay and 90% on HAART with undetectable HIV.

“Little or no data has been published on the ability of HIV positive individuals to respond to [the quadrivalent HPV vaccine] Gardasil,” he commented. “Can they make an appropriate serological response, and which subgroups will not benefit?”

First - 'type' the virus

The study therefore took serological tests of study participants to see if they had antibodies to HPV types 16 and 18. These, the two most common ‘high risk’ varieties of HPV, cause 70% of cases of anal and cervical cancer, and the available HPV vaccines Gardasil and Cervarix produce a high level of protection against these strains for individuals who are not already infected with them. In addition Gardasil protects against infection with HPV types 6 and 11, which cause 95% of non-cancerous warts.

Step 2 - anal smears and screening

The patients also had an anal smear for precancerous cells and an anal screen for HPV DNA, which indicates actively reproducing virus.

Step 3 - vaccinate

The patients were then given an initial dose of Gardasil.

The second and third doses of Gardasil were given at month two and month six, and tests taken again at month seven for antibodies to HPV, HPV DNA and precancerous cells.

Step 4 - did it work?

Results showed that 34% of the men in the study had antibodies to HPV-16, 6.4% to HPV-18 and 3.2% to both. Perhaps surprisingly, this means the majority of individuals (56.5%) did NOT have antibodies to the two strains of HPV with the highest risk of anal and genital cancers.

Sixty-three per cent of men had HPV DNA (of any high-risk type) detectable in anal samples, and 22.6% of men had HPV DNA from types 16, 18 or both. This means that 40% of men had active infections with other high-risk types of HPV (if it is not type 16 or 18, there is much slower progression to cancer).

Recent or prolonged infection?

Berman commented that the men with detectable DNA could either be men with relatively recent infection and a normal antibody response, or men with prolonged infection and a delayed or non-existent antibody response. The latter are at most risk of developing cancer.

In HIV negative people antibodies to the infecting subtype of HPV develop within 6-9 months of infection and then clear the infection from the body. This process is delayed and drawn out for longer in people with HIV, which probably causes the higher rates of anal cancer.

Abnormal cells

Twelve individuals had abnormal anal cells, six of whom had precancerous cells. Of the twelve, ten had detectable HPV DNA, three of whom had HPV-16, three were co-infected with HPV-16 and HPV-18, and four had types other than 16 or 18.

Of the 25 individual with antibodies to HPV-16, ten (40%) had detectable DNA from this strain detected in samples, in addition to three of the individuals who did not have antibodies to HPV-16, and two men without antibodies to HPV-18 had detectable DNA from this strain. Altogether 11% of patients had both antibodies to HPV16 or 18 and evidence of the genetic material of these strains, indicating a complete or ineffective antibody response.

Vaccinate to boost chances of prevention and getting rid of infection

In answer to a question, Berman commented that it was possible that giving such men the HPV vaccine might stimulate a much stronger response which might result in clearance of infection “but Merck (Gardasil’s manufacturers) have absolutely no data on the efficacy of giving their vaccine to people with an existing infection.”

Altogether, 53% of men had evidence of neither exposure nor infection with HPV-16 or HPV-18 and were therefore likely to derive substantial benefit from Gardasil as long as HIV infection does not impair the immune response, while another 35% had one of the strains and would therefore benefit at least from vaccination against the other one.

Becker commented that the proportion of men with antibodies to HPV16 was higher than reported previously. However since 40% of men had indications of active infections with subtypes other than HPV-16 or 18, second-generation polyvalent vaccines should be developed.

Source and references

Permalink

---