By Emily Newman
A CDC recommendation report issued by the Advisory Committee on Immunization Practices released late this summer calls for a better understanding of anal cancer development and screening among a population at high risk—men who have sex with men (MSM). Although there’s still uncertainty about the best way to screen for and treat anal cancer, here’s what we know right now about who gets it, and what to look out for if you’re worried.
Most often, anal cancer is caused by human papillomavirus (HPV), a sexually transmitted infection that takes up residence in the outermost layer of the skin or mucous membranes. This virus is stunningly common—the most prevalent sexually transmitted infection in the U.S. Every year, 14 million new people get infected, with an estimated 79 million people infected in total. There are over 150 different kinds of HPV spread through skin to skin contact—about 40 of which infect the genital tract. The ubiquity of HPV and ease of transmission means that people who end up getting HPV usually do so when they’re young and with one of their first sexual partners.
Most of the time, HPV infection goes undetected and doesn’t cause any health problems. Out of the 150 different types of the virus, only a few are known to cause clinical symptoms. Some strains of HPV, such as types 6 and 11, cause genital warts which can form in or around the genitals or anus. While likely to be a source of stress and discomfort, genital warts generally don’t progress to cancer. They’re considered by clinicians to be clinically benign—while they may be annoying, they won’t kill you.
Other strains of HPV can be dangerous. Two types of HPV, types 16 and 18, are known to cause cancer of the cervix, vulva, penis, and anus. People with HPV who go on to develop cancer first develop abnormal skin growths called high-grade squamous intraepithelial lesions (HSILs). These pre-cancerous growths, when left untreated, can go on to develop into cancer.
Men who have anal sex with men (MSM) are more likely to get anal HPV than men who only have sex with women. Researchers estimate that the prevalence of anal HPV among men who only have sex with women is around 15% while anal HPV prevalence for MSM is around 60%. If you add HIV into the mix, infection risk goes up still—one study published by HIV Medicine found that 77% of MSM with HIV were also infected with anal HPV; another study published by the Journal of Infectious Diseases found that over 90% of MSM with HIV were infected with at least one strain of HPV.
This increased risk extends to the strains of HPV known to cause cancer, with about a third of MSM living with HIV shown to have HPV type 16. MSM with HIV are also more likely to go on to develop anal cancer, with incidence rates per person-years as high as five times that of HIV-negative MSM. According to the CDC, men who have sex with men are about 17 times more likely to develop anal cancer than men who only have sex with women.
Does this mean that HIV somehow causes or makes someone more susceptible to being infected with HPV?
Probably not, says Joel Palefsky, MD, a clinician and researcher at the University of California, San Francisco, and the president of the International Papillomavirus Society and International Anal Neoplasia Society. He explains that people with HIV probably get infected with HPV first, but that HIV’s effects on the immune system make it more likely for HPV to stay active and cause health problems.
“When you’re healthy, with a good immune system, you control the virus very well—to the point where it’s not detectable using currently available tests—so it seems like you’re HPV negative. But if you get HIV, your immune system doesn’t control HPV as well. And if you become immune suppressed later, the virus that was previously quite harmless can potentially reactivate and start to cause some of the diseases we’re talking about,” explains Palefsky.
The number of men who have sex with men that develop anal cancer stemming from HPV infection is on the rise—especially among men living with HIV. Over the past ten years, the number of new anal cancer cases has increased by about 2.2% each year. Palefsky speculates that this trend is due to the increased lifespan conferred by better and better HIV treatments.
“Going from HSIL to cancer takes time—decades in some cases. Antiretroviral therapy provides the opportunity to live long enough for that to happen. In settings where people are living long but not necessarily being screened or treated for HSIL, then we think that gives people the opportunity to develop cancer which they may not have had in the past,” he says.
Screening for HPV—either cancer-causing types or otherwise—is not currently recommended. “In part because HPV is so common, and also because doing a test isn’t going to provide a whole lot of useful information on which we can act,” explains Palefsky.
There are a few things people can do if they’re concerned. The first is for people under the age of 26 to get an HPV vaccine. Gardasil, the same HPV vaccine women receive to prevent cervical-cancer causing forms of HPV, is approved for men. It is highly effective in preventing HPV type 16 and 18 infections. Palefsky hopes that it will become routinely administered to boys and girls in the same way that vaccines for measles or mumps are provided to everyone of a certain age. After the age of 26, the vaccine probably won’t be as helpful since most people will have already been exposed to the forms of HPV the vaccine protects against.
People who haven’t had the HPV vaccine should be on the lookout for persistent symptoms in the anus that aren’t due to other medical issues like hemorrhoids or a herpes outbreak. “If you’re having pain or bleeding, or a bump that’s otherwise unexplained then you should seek immediate medical attention,” explains Palefsky.
Palefsky also recommends that men who have sex with men, especially those living with HIV, have an annual digital ano-rectal exam (called “DARE”). This type of screening test, along with anal cytology screening to test for pre-cancerous cells, is used to detect early stages of anal cancer. Assuming that providers have the knowledge and resources needed to comprehensively assess and treat patients who come back with abnormal cytology results, early detection of precancerous or cancerous cells is key to better treatment outcomes.
“It’s a chicken and egg kind of situation right now. We haven’t yet established that the procedures to detect anal pre-cancers and early signs of anal cancer should be standard of care. This is because we don’t have firm evidence that they are beneficial. Our approach at the UCSF Anal Neoplasia Clinic, Research, and Education Center is to assume that early screening is beneficial until research tells us otherwise,” notes Palefsky.
Palefsky is currently undertaking a large-scale clinical trial to help investigate this very question. The new study—called ANCHOR—will help determine what the best course of action for people with HSIL actually is. “When all is said and done, the only reason to be screening and treating HSIL is to reduce the risk of anal cancer. But because nobody has done a randomized controlled trial before, nobody can say with certainty that what we’re doing actually helps. For instance, I have many patients that—when I treat their high grade disease—don’t get cancer. But I can’t say for sure that it’s because of what I did. It’s possible that they never would have developed cancer even if I did nothing.”
The study will enroll people in 15 sites around the country living with HIV who are found to have, through a biopsy, anal HSIL. Study clinicians will then treat or actively monitor the lesion using study protocol guidelines, and progression from HSIL to cancer will be evaluated. If successful, the ANCHOR study will inform the development of clinical guidelines for the screening and treatment of HSIL.
“This study is going to be an incredibly important study for the HIV-positive community,” notes Palefsky. “It’s a major investment by the National Cancer Institute for the health of HIV-positive people including LGBTQ folks. We’re fortunate to be in a place where we now have a different set of problems to deal with for people with HIV—problems with aging and chronic diseases. This is a great time to get a handle on those.”