The HIV Clinicians’ Society recently had the honor of hosting a talk by Prof Stephen Hawes from Washington University. Thanks to our friends at I-TECH, Namibia (who technical work for the Washington U Department of Global Health), Hawes gave a presentation about his work with HPV, HIV and Cervical Cancer in Senegal. Given the popularity of the HPV vaccine (you see the posters in practically every doctor’s consulting room here) and the fact we actually charged a fee for attendance (people here seem to appreciate that which costs them something more than freebies), we had a huge growd of clinicians in the audience.
Hawes began the presentation by really charting the fundamentals of HPV. He explained that is a sexually transmitted virus that consists of way more thna 200 hundred different HPV virus subtypes, denotated by numbers. HPV 16, from what I recall, is one of the two types that accounts for more than 70% of all cervical cancer cases. Though everyone in the audience was aware of the relationship between HPV and cervical cancer, Dr Hawes really did take the time to take us through the story, using epidemiological terms, that link the two.
In brief, Hawes explained how HPV is an STI that most women acquire shortly after sexual debut, during adolescence or the early twenties, but one that most women soon clear thereafter. I remember seeing the graph of HPV seroprevalence (that is presence of the HPV antigen – not the anti-HPV antibody, since the presence of the antibody does not indicate persistant infection) versus age of woman and this what stuck: infection rises sharply in adolescence and peaks in the mid twenties before falling steadily with age. So HPV is not like HIV that once acquired remains. Most of the time, it is cleared by the body. This sometimes mean the virus enters a latent – ‘dormant’ – state in the body and is undetectable. The take home message of that graph, though was how the prevalence of cervical cancer grew steadily with age, as the prevalence of HPV infection fell in women past the middle age (though he did mention his current graduate student was researching HPV infection among women in their middle ages who resume a dating life after divorce). What happens is that only those women with persistant HPV infection are those who develop the cancer.
Hence the pap smear programs that have been instituted in many developed countries and which have had tremendous success in the reducing the incidence of HPV in the US. Hawes showed us cervical cancer incidence in the US over the decades since the 1950s and though he conceded that other factors may have been operating in the population of women during those fifty years, it is generally accepted the pap smear program has reduced the incidence of this cancer through early detection.
Hawes did dedicate quite a large chunck of the talk describing the pathology of the cervical cancer from HPV infection, to the pre-cancerous lesions and up to the appearance of cancer in the cervix, including the various methods of ‘ablating’ or remove the cancerous areas and the advantages and disadvantages of the different methods. I will omit this section, because frankly you can find that in your med school textbook.
What was most interesting was the research he and his group have been doing in Sengal since the late 80s. They have been doing prospective studies (that is following a group or ‘cohort’ of women) in Senegal in order to elucidate the risk factors for cervical cancer. Clearly, HPV infection was one of them, but the thrust of his talk was not on demonstrating this already known relationship. On the other hand, he focused on how HIV-1 and HIV-2 infection were associated with progression to cervical cancer. Using unequivocal results, like the odds ratios of the order of 10, he showed how HIV infection was a potent risk factor for progression to cervical cancer. He did point out that in the clinics where he found the patients, they did treat each and every one of them when they presented with the tell tale ‘high grade’ lesions just before cancer. However, I still wondered whether they would be able to do the same study in developed countries, where doctors remove any lesion that would even indicate the approach to cancer. I wonder to what extent their data depended on working on a ‘resource poor’ setting where pap-smears are not the norm.
Of course, they were able to get the data they had because a non-trival fraction of their cohort was HIV-1 or HIV-2 positive. The women in the cohort were married, had many children, (a median 6) and some of them were in polygamous marriages and none of them had university level education. My impression was that these women victims of a society that allows men sexual liberty (prostitution is legal) while the women have basically no control over their reproductive lives.
What I found fascinating was that although he did not present data on women who were on HAART (it is in the pipeline), he did show that women with HIV-2 who had no immunosuppresion, as is typical with HIV-2, also had just as high a risk of developing cancer. The take home message: We are sitting on a ticking time bomb in Namibia as more and more HIV infected women live longer, their chances of developing cervical cancer become astronomically high.
He did present data from Namibia, collected by the Global Cancer database or something or the other, which showed cervical cancer to be the second most common cancer among women after breast cancer. He also showed that as for HPV, there is no data in Namibia on the prevalence of overall HPV infection, let alone the prevalence of the two leading carcinogenic types. After the talk, he said that it would be good to have this data so that policy makers can see the actual facts about HPV infection here, even though that among the medical community, there is no doubt that HPV infection is driving cervical cancer here, given the similarity of our setting here to that of other countries in the region where HPV prevalences are known.
So there were questions from the doctors which were also fascinating. The first question asked about men – where do they fit into this picture. Hawes explained that HPV stays on the penis for a very short amount of time, about two weeks, and that it did not cause the same pathology as in the cervix. The exception to this is men who have sex with men, where HPV infection of the anus follows a very similar to that of the HPV infection in the cervix, leading to anal cancer. He said for this reason, young boys, unlike young girls, are not the target for the HPV vaccine. ‘It is very difficult to determine whether a young boy will be a man who has sex with men, so it is not possible to vaccinate that [vulnerable male] population.’
There was some other questions, but I do not remember them now. What I did find interesting though was that Hawes spoke about how the vaccine is a preventative one and is not recommeneded in the event a woman is already infected with HPV. However, after the talk I spoke with one doctor who said he gives the vaccine to his patients when he sees there is an ‘abnormality’ in the cervix and it clears away. So is there a disconnect between what is recommended and what is happening in practice?
That would be for you to say, your are the clinicians working in the field, leave your comments below. It would be much appreciated.