Since HIV patients started receiving antiviral treatment (HAART or cART), HIV has become a chronic disease for many people. Because HIV patients are generally living longer, new conditions are emerging. One of the most striking is anal cancer. Anal cancer is becoming increasingly common, particularly among HIV-positive men with same-sex contacts (MSM), but HIV-positive women are also at increased risk.HPVLike cervical cancer, anal cancer is caused by HPV (human papillomavirus). There are more than 100 types of this virus, most of which are harmless. However, a few types are capable of causing cancer. These so-called "oncogenic" HPV types are found in both cervical and anal cancer. Most people will encounter one or more (oncogenic) HPV types during their lives. The major difference with HIV-negative people is that HIV-positive people have much more difficulty clearing HPV, even when treated with antiretroviral drugs. This means that an infection with oncogenic HPV persists for years, which in some cases can lead to cancer.ANAL SEXPassive anal sex is a risk factor for anal HPV infection. The vast majority of HIV-positive MSM are diagnosed with an anal HPV infection, usually consisting of multiple (oncogenic) types. However, anal sex is not a prerequisite for an HPV infection. Even people who don't engage in anal sex can easily contract an anal HPV infection.AINAIN (Anal Intraepithelial Neoplasia) refers to changes in the mucous membrane in and around the anus. AIN involves abnormal cells in the mucous membrane. These abnormal cells can potentially develop into anal cancer, and for this reason, AIN is considered a precursor to anal cancer.
Low-grade AIN (AIN 1) is often harmless, but can develop into high-grade AIN over time. High-grade AIN (AIN 2 and 3) often does not resolve spontaneously and can develop into anal cancer. AIN is found in the majority of HIV-positive MSM. This does not mean that all these men will develop anal cancer. Ultimately, AIN will develop into cancer in a two-thirds minority. Unfortunately, it is not yet well known how often and in whom AIN develops into anal cancer.
DIAGNOSTICS OF AIN
Precancerous lesions of cervical cancer (CIN) can be detected with a Pap smear. A Pap smear does not seem to be useful for detecting AIN in HIV-positive MSM. The diagnosis can only be made with a biopsy (a small sample of the anal mucosa). This is performed using High Resolution Anoscopy (HRA), which allows for detailed examination of the anal mucosa under magnification. Biopsies of any suspicious lesions are then taken for further examination by a pathologist.
TREATMENT OF AIN
The current standard treatment is electrocoagulation (burning), and a recent study at the AMC (Amsterdam Medical Center) clearly shows that this treatment is more effective than the creams imiquimod (Aldara) and 5-fluorouracil (Efudix). However, if the lesions are located on the external surface of the anus (in a minority of cases), imiquimod is preferred. Other options include laser, nitrogen, freezing, and acetic acid. Unfortunately, few good studies have been conducted on other treatments, and the results are still disappointing. For all treatments, only a subset of patients respond well to treatment, and AIN often recurs.
Vaccination: preventive and therapeutic.
There are two forms of HPV vaccination. The most common is prophylactic or preventive HPV vaccination, which requires vaccination before someone comes into contact with HPV. This is the case with the government vaccination program. This involves the use of the HPV vaccine Cervarix, which is used to vaccinate 12-year-old girls to prevent cervical cancer.
Prophylactic HPV vaccination has been shown to prevent AIN in a select group of young HIV-negative MSM. The question is whether prophylactic vaccination is beneficial for HIV-positive MSM. Most have already been exposed to or carry multiple (oncogenic) HPV types, making prophylactic vaccination potentially unnecessary. Several hospitals in Amsterdam, including the AMC, have launched a study into the effectiveness of Gardasil vaccinations in preventing new high-grade AIN after patients had already received adequate treatment.
Another vaccination method is therapeutic vaccination. A therapeutic vaccine targets a different part of the immune system, and the advantage is that it can be administered if someone is already infected with HPV or already has AIN. This is an attractive alternative to the current, often burdensome and moderately effective treatment options. So far, one study has shown some effectiveness in high-grade AIN. A study has been initiated at the AMC to investigate the effectiveness and safety of therapeutic HPV-16 vaccination for high-grade AIN.
Future:
Given the increase in anal cancer and the similarities between anal cancer and cervical cancer, diagnosing and treating AIN in people with HIV seems important. In the Netherlands, only a few centers have experience with high-resolution anoscopy (HRA). Therefore, more staff need to be trained in detecting AIN using HRA. Before HRA can be routinely offered, it is important to gather more data on optimal diagnosis, treatment, and risk factors.
AIN screening in Amsterdam.
It is currently too early and logistically impossible to screen all HIV-positive patients in the Netherlands for AIN. Therefore, a smaller-scale collaboration has been established in Amsterdam between the AMC, the OLVG, the Slotervaart Hospital, and the DC Klinieken Oud Zuid. Doctors and nurses have been trained in High Resolution Anoscopy. This allows HIV-positive men to be screened for AIN at these centers. |
