Surgeons Call for More Aggressive HPV Screening in Gay Men

Surgeons Call for More Aggressive HPV Screening in Gay Men In Contrast, CDC Guidelines Do Not Support Regular Screening Christina Frangou   Seattle—It’s time for better care standards for men who have anal sex, say experts who study these men. “Surgeons need to face the fact that this is a significant segment of the population who has specific problems that need to be confronted,” said Stephen E. Goldstone, MD, assistant clinical professor of surgery at Mount Sinai School of Medicine in New York City and author of The Ins and Outs of Gay Sex, a medical handbook for gay men. Since the late 1980s, research has been building that suggests men who have sex with men could benefit from specialized screening programs to test for human papillomavirus (HPV). However, support for such a program has been limited to a small minority of healthcare practitioners. Now the case for more aggressive screening, better follow-up and treatments designed specifically for men who have sex with men is becoming too strong to ignore, say advocates. “Anal cancer rates are rising quickly, especially in gay men. The old saying that 'oh, I live in Missouri or wherever—we don't have gay people’ is wrong. [Male] patients who have sex with men are a growing problem, and we cannot confront it by ignoring it. These patients deserve the same quality of treatment that we offer to women,” said Dr. Goldstone. Dr. Goldstone is an openly gay surgeon and one of a growing group of specialists that want surgeons, primary care doctors and colorectal specialists to improve the quality of care provided to men who have anal sex. They want to see increased screening for HPV and more aggressive treatments offered to men who have precancerous lesions. (Dr. Goldstone also noted that surgeons should ask women about sexual practices and screen them for HPV if they have anal sex. Anal cancer was historically a disease of women who probably either caught HPV from anal sex or autoinfection from their vaginal canal, he said.) “No one knew that cervical cancer was preventable before the use of Pap smears became widespread in the 1960s and cut the incidence of the disease by 80%. The hope is that a simple, early screening procedure for HPV-induced anal cancer would lead to a similar drop in disease and death,” said Joel Palefsky, MD, professor of medicine and author of several studies on HPV in men, University of California at San Francisco (UCSF) School of Medicine. Studies show that anal cancer is much more common among gay men than the general population. Available statistics indicate that up to 35 gay men per 100,000 develop anal cancer per year. In comparison, the risk in the general population is 0.9 per 100,000. For most men, there is no need to treat HPV because the vast majority never develop health problems from the virus. Opponents of specialized screening for men who have sex with men say this makes regular screening unnecessary. Advocates for screening argue that a minority do develop significant problems. Men with high-risk HPV types have a higher risk of getting anal cancer. HIV-positive men with HPV are more likely to get severe and prolonged cases of genital warts, which may be more resistant to treatment. They also are more likely to develop anal cancer. Regular screens can detect any cell changes that can be treated before they lead to cancer, said Dr. Goldstone. At the 2006 annual meeting of the American Society of Colon and Rectal Surgeons (ASCRS), held in June, a panel of surgeons and internists who specialize in treating this population called for surgeons to increase screening for HPV in these men. Dr. Palefsky said HIV-negative men who have sex with men should be tested every two to three years, based on results of cost-effectiveness modeling done by the UCSF research. If the cytology is positive, the men should be referred for high-resolution anoscopy with biopsy. HIV-positive men require annual testing, followed by high-resolution anoscopy studies and biopsy in patients with abnormal cytology, he said. Major stakeholders in the healthcare policy debate do not support regular anal screening for men who have sex with men. Notably, the Centers for Disease Control and Prevention (CDC) restated its opposition to regular screening in a March 2006 update of treatment guidelines on HPV-associated cancer (www.cdc.gov/std/hpv/STDFact-HPV-and-men.htm). The guidelines note that currently no tests are approved for detection of early evidence of HPV-associated cancers in men. “It is not yet clear that finding and removing abnormal cells from the anus will effectively prevent anal cancer from developing in the future. CDC does not recommend anal cancer screening,” the statement reads. “It’s complicated,” said J. Michael Berry, MD, an assistant clinical professor of medicine at UCSF. “The prevalence of HPV infection among men who have sex with men, especially those who are HIV-positive, is so high that HPV screening doesn’t add anything to your clinical management. Anal cytology screening is only useful if someone can manage abnormal results.” Surgeons or any health practitioners to optimally treat men with HPV need to learn to recognize the lesions by using high-resolution anoscopy, he said. High-resolution anoscopy “is the foundation on which screening and treatment of precancerous lesions is based.” Drs. Berry and Palefsky and their research team pioneered the use of high-resolution anoscopy to manage patients at risk for anal cancer. They describe it as colposcopy of the anus and perianal region that can identify and treat precursors to anal cancer. Too few physicians are trained and experienced in performing high-resolution anoscopy, said Dr. Berry. “This is an incredible tool for examining patients with anal disease, but physicians who are not trained will do a substandard job.” More healthcare providers, especially surgeons, are learning high-resolution anoscopy, he said. In the past year, experts on the technology have conducted educational courses at the American Cancer Society and ASCRS annual meetings, and have been asked to do more. “Physician attitudes about this are changing. People are attending more courses and express more interest in learning how to treat this population,” said Dr. Berry. He advised colorectal surgeons who are not trained in high-resolution anoscopy to work with other healthcare providers who are. Dr. Goldstone said men should be monitored carefully for any precancerous areas or warts and undergo targeted treatment whenever possible. “We’re trying to advocate the same treatment principles that you use for women in men. The only difference is that in women you can remove the cervical transition zone through surgery. We can’t do that in men. Instead, we’re talking about targeted destruction of lesions.” Surgeons traditionally carry out excision, electrocautery, laser ablation and cryotherapy, or topical treatments like trichloracetic or dichloroacetic acids, to treat warts or significant lesions. Newer methods are also being studied. Researchers have shown that infrared coagulator ablation of high-grade anal squamous intraepithelial lesions is an effective, safe, office-based treatment for anal squamous intraepithelial lesions. In a retrospective study of 75 HIV-negative men who have sex with men with 113 primary lesions who underwent ablation, 81% of lesions were cured after the first treatment, and 93% were cured after a second treatment. No patient developed squamous cell carcinoma. “This is a therapy that is ready for prime time. Treating these lesions is not that different from treating other lesions, and a lot of surgeons already use the [infrared coagulator],” said Dr. Goldstone, the lead investigator on the study. He used the IRC 2100 Infrared Coagulation System by Redfield Corporation (Rochelle Park, N.J.). Recurrence rates did not change over the three years of study (2002-2004), and there appears to be no learning curve with the treatment. Patients tolerated the procedure with at most a mild oral narcotic analgesia. There were no cases of infection, bleeding or anal stricture. An earlier study showed that infrared coagulator ablation was also effective in treating HIV-positive men, although not as successful as in the HIV-negative group (Goldstone SE et al. Dis Colon Rectum 2005;48:1042-1054). HIV-positive men were twice as likely to have a lesion persist after their first infrared coagulation treatment (P=0.026) and 1.7 times as likely as the HIV-negative patient to develop a metachronous lesion after their first treatment (P=0.147). Surgeons should treat lesions using the method they are most comfortable with, said Dr. Goldstone. He stressed the importance of checking patients with anal warts carefully and performing a thorough anal exam. Any warts that appear unusual should be biopsied, he said. “If a patient comes to a surgeon and has anal warts or rectal bleeding, a surgeon needs to be mindful that there could be a precancerous condition going on,” he said. There is also growing evidence that a vaccine may be able to prevent genital warts and precancerous genital lesions due to HPV. In clinical trials conducted at UCSF, investigators found that a vaccine made from the E7 protein of HPV type 16 fused to a protein from a bacterium, known as SGN-00101, is safe for use in men and women with high-grade anal intraepithelial neoplasia. Some patients had regression of their anal intraepithelial neoplasia, but investigators said the study was not powered to evaluate efficacy (Palefsky JM et al. AIDS 2006;20:1151-1155). The vaccines did not affect viral loads in the HIV-positive patients. In June, Gardasil (Merck), a different HPV vaccine, was approved by the FDA for use in females aged 9 to 26 years. This is a preventive vaccine and protects against the four most common types of HPV: 6, 11, 16 and 18. It is currently being studied for efficacy in men. Experts emphasized the need for close follow-up of men with precancerous anal disease. “Recurrence is a real problem, but keep in mind [that] we can now treat these men effectively in the office. Surgeons have a very definite role in management of this, but a large part is following these patients carefully to detect and treat their recurrences in the office,” said Dr. Berry.