No consensus screening guidelines exist for human papillomavirus (HPV)–related cancers other than cervical cancer. As a step toward establishing such guidelines, studies under way or in the planning stages at The University of Texas MD Anderson Cancer Center will test various strategies for early detection of specific HPV-related cancers in populations believed to be at high risk.
Although HPV is known to cause oropharyngeal, penile, anal, cervical, vaginal, and vulvar cancers, only cervical cancer has established screening guidelines and a reliable test—the Papanicolaou (Pap) test—that can detect early cancer or precancerous dysplasia. “The Pap test can detect precancerous tissue and prevent cervical cancer,” said Erich Sturgis, M.D., M.P.H., a professor in the Department of Head and Neck Surgery and the Department of Epidemiology. “But we don’t have such a test for oropharyngeal or anal cancer.”
Dr. Sturgis and his colleagues hope to provide data for such tests in clinical trials that will screen people at high risk for HPV-related anal or oropharyngeal cancers. One such trial is currently enrolling women, and another will soon begin enrolling men.
Screening for anal cancers in women
Patients who have HPV-related cervical, vaginal, or vulvar carcinomas are believed to be at high risk for HPV-related anal carcinoma; however, the rates of anal cancers in these patients remain unclear. An ongoing clinical trial seeks to determine the prevalence of anal cancer in women who have cervical, vaginal, or vulvar cancer or dysplasia and compare methods of screening for HPV-related anal cancer and dysplasia.
The clinical trial, known as the Prevalence of Anal Dysplasia and Anal Cancer in Women with Cervical, Vaginal, and Vulvar Dysplasia and Cancer (PANDA) trial (No. 2014-0021), is now enrolling patients at MD Anderson, its regional care centers, and Lyndon B. Johnson Hospital in Houston.
Kathleen Schmeler, M.D., an associate professor in the Department of Gynecologic Oncology and Reproductive Medicine, and Craig Messick, M.D., an assistant professor in the Department of Surgical Oncology’s Section of Colon and Rectal Surgery, are the co–principal investigators of the PANDA trial. “Dr. Messick and I share several patients with both anal and cervical or vulvar cancer, and this made us realize that maybe we should be screening women with gynecological cancers for anal cancer,” Dr. Schmeler said. “That’s why we’re doing this study.”
Dr. Schmeler said that current anal cancer care, without standardized screening, is similar to the state of cervical cancer care before the advent of the Pap test. “Most of the time, people are diagnosed with anal cancer when it is symptomatic, after the cancer is advanced and has led to another problem,” she said. “That’s how cervical cancer used to be, but since the Pap test became standard, we’re finding cervical cancer in the preinvasive phase or at an early stage. We’d like to do the same thing with anal cancer.”
The PANDA trial eventually will enroll 500 patients. Eligible for the trial are women 18 years or older who have invasive squamous cell carcinoma or high-grade dysplasia of the cervix, vagina, or vulva. Excluded from the trial are women who are pregnant or have a history of dysplasia or invasive carcinoma of the anus or anal canal.
In addition to the standard tests related to their gynecological cancer or dysplasia, patients in the study undergo screening for anal cancer or dysplasia by an anal Pap test, anal HPV test, and high-resolution anoscopy. Patients with abnormal findings on any of these screening tests are referred to Dr. Messick’s group for further evaluation and care.
Besides showing the prevalence of HPV-related anal dysplasia and cancer in this high-risk population of women, data from the study will provide information about the sensitivity and specificity of anal Pap tests, anal HPV tests, and anoscopy. “We know there are women at high risk for anal cancer,” Dr. Schmeler said. “We want to find out how often and the most effective way to screen these women.”
Screening for oropharyngeal cancers in men
As the PANDA trial seeks to provide data that could lead to routine screening guidelines for HPV-related anal cancers, Dr. Sturgis is helping organize a trial to provide similar data for HPV-related oropharyngeal cancers. Because both oropharyngeal HPV infections and HPV-related oropharyngeal cancers are more common in men than in women, Dr. Sturgis’s trial will enroll men only, specifically those in their 50s.
The trial will soon begin enrolling participants at several locations in the Houston area. Participants will fill out a questionnaire about tobacco and alcohol use as well as sexual behavior, and cell samples for HPV testing will be obtained from the throat with a “swish and spit” technique. Blood will also be drawn to test for antibodies to early (E) antigens of HPV type 16 in the serum.
“Our previous research showed a very strong link between antibodies to HPV-16 E6 and E7 antigens in the serum and oropharyngeal cancer,” Dr. Sturgis said. “We estimate that 1%–2% of the men in our trial will test positive for these antibodies.”
Men whose serological tests are positive for antibodies to HPV-16 E6 or E7 antigens will be sent to MD Anderson for further HPV and cancer screening, as will an equal number of men who test negative for the antibodies. Both groups will undergo standard clinical examinations of the throat, anus, and penis and standard ultrasound examination of the neck lymph nodes. The anal exams will include standard high-resolution anoscopy and a newer technique, high-resolution microendoscopy, as well as selective brushings to obtain cells for standard and novel HPV tests.
The main focus of the trial, however, will be oropharyngeal cancers. “We will use some experimental approaches to see if imaging can identify early oropharyngeal cancers before they are visible to the naked eye,” Dr. Sturgis said. One technique that may be used in the study, optical coherence tomography, is commonly used in ophthalmology but not to detect oropharyngeal cancers. Another, narrow band imaging, has been used with endoscopy to detect early gastric tumors.
The study will also involve taking cell samples from the tonsils and the base of the tongue to look for HPV that has been integrated into the human genome. Integrated HPV is typically the first step of tumorigenesis in HPV-related cancer. Dr. Sturgis said, “This will be the first screening application of testing for integrated HPV.”
Participants will be followed up for 5 years. The head and neck examination and imaging studies will be repeated every 6 months, but the anal and penile tests will not be repeated.
The two goals of the trial are, first, to see whether serological HPV testing in a high-risk group is an effective screening tool and, second, to see which tests are most effective for detecting early HPV-related cancers or precancers. Dr. Sturgis said, “The central question is, can we establish a screening mechanism for HPV-related oropharyngeal cancer?”
Encouraging HPV testing
Other MD Anderson researchers are looking into the role of HPV testing in cancer screening and prevention. In one trial scheduled to begin enrolling patients this fall (No. 2015-0795, led by Jessica Hwang, M.D., an associate professor in the Department of General Internal Medicine), patients who have received allogeneic stem cell transplants will undergo HPV testing in the anatomic areas associated with HPV-related cancers. Studies have shown that such patients are at a high risk of HPV-related cancers.
Dr. Hwang’s study, together with the studies led by Dr. Sturgis and Drs. Schmeler and Messick, may provide data that will enable the early detection of HPV-related cancers. In the meantime, Dr. Sturgis urges physicians to encourage men in their 50s to participate in his trial.
Likewise, Dr. Schmeler said she hopes physicians will encourage their patients who have had one HPV-related gynecological cancer to consider participating in her clinical trial. “Since there are no guidelines for anal cancer screening, this study is a good option for physicians with patients who are at risk.”
For more information, call Dr. Jessica Hwang at 713-745-3559, contact Dr. Craig Messick at 713-445-1544 or firstname.lastname@example.org, contact Dr. Kathleen Schmeler at 713-745-3518 or email@example.com, or call Dr. Erich Sturgis at 713-792-5432.
To learn more about ongoing clinical trials at MD Anderson, visit www.clinicaltrials.org.
OncoLog, August 2016, Volume 61, Number 8