HPV Oncogenic in Head and Neck and Anal Cancer

For some time, medical science has recognized that the human papilloma virus (HPV) causes nearly all cases of cervical cancer. It is becoming increasingly evident that certain strains also play a major role in head and neck cancer and anal cancer. At the 15th Annual Meeting of the National Comprehensive Cancer Network (NCCN), experts discussed “HPV and the Risk of Cancer,” addressing HPV-related cancers and the importance of vaccination as a preventative measure.

Robert J. Morgan, MD, City of Hope Comprehensive Cancer Center, started out by describing cervical cancer as “one of the major success stories in medicine prevention,” in the United States, which has seen the number of cervical cancer cases and related deaths decline in the past decade. Worldwide, however, the story has not been as positive and Morgan said “there is substantial mortality” in many countries. While Morgan identified HPV strains 16 and 18 as responsible for 70% of cervical cancer cases, he said there are 19 high-risk strains. The existing vaccines protect against 2 to 4 of these (depending on the vaccine). Several clinical trials have demonstrated the safety and efficacy of these vaccines in preventing genital warts in both sexes and cervical dysplasia and cervical carcinoma in women.

Remaining questions, Morgan said, include whether males should be vaccinated, the age at which to start vaccinating, how to make vaccinations more available internationally, and affordability. As evidence accumulates of the connection between HPV and other types of cancers that affect men, studies will likely have to consider the cost-effectiveness of vaccinating males against HPV. At present, neither FDA-approved HPV vaccine is indicated for the prevention of any cancer other than cervical.

David G. Pfister, MD, Memorial Sloan-Kettering Cancer Center (MSKCC), said HPV 16 is responsible for most cases of HPV-positive head and neck squamous cell carcinoma (HNSCC). The prognosis for HPV-positive HNSCC is better than the prognosis for HPV-negative HNSCC, which is often related to alcohol and tobacco use. Pfister said while declining alcohol and tobacco use in Europe and the United States has led to a lower rate of HPV-negative oropharynx cancer, the rate of HPV-positive oropharynx cancer has increased. Patients with HPV-positive HNSCC tend to be younger than individuals with HPV-negative HNSCC and are more likely to be white. Risk factors include a greater number of sexual partners and certain sexual practices, such as oral sex. People with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome are also at greater risk of developing HPV-positive tumors, particularly tonsil lesions.

“At this point and time,” said Pfister, “HPV-positive and HPV-negative tumors are essentially treated the same way.” But there is a vast difference in prognosis between HPV-positive and HPV-negative disease, Pfister said, because HPV-positive tumors are more sensitive to treatment. The 2-year overall survival rate for patients with HPV-positive oropharynx tumors is 94% compared with 58% for those whose tumors are HPV negative (P = .004). The disparity has led MSKCC to consider designing studies specifically for patients with HPV-positive tumors. Pfister said survivorship issues are also important to examine because of the younger patient population, and he would like to see more information disseminated to patients.

J. Michael Berry, UCSF Helen Diller Family Comprehensive Cancer Center, discussed HPV-related anal cancer. Berry disclosed that he is a subinvestigator for HPV vaccine studies and his institution receives research grants from Merck & Company, which manufactures the Gardasil vaccine. Gardasil is not approved by the FDA to prevent anal cancer, Berry said. Preventing anal infection with HPV 16 and 18, however, may decrease the incidence of anal cancer by at least 70%. As Pfister indicated with HNSCC, Berry said anal HPV infection is more common in HIV-infected persons; studies suggest gay men with HIV constitute the highest risk group. Anal HPV infection is also more prevalent in women who have a history of high-grade cervical neoplasia or an HPV-related gynecologic cancer.

Berry advocates the use of high-resolution anoscopy to identify high-grade anal intraepithelial neoplasia (HGAIN). “HGAIN are potentially precancerous, and eradication of these lesions has been proven to effectively prevent anal cancer,” Berry said. High-resolution anoscopy involves soaking the anus in 3% to 5% acetic acid, examining it carefully with a colposcope, and biopsying abnormal areas. Berry’s clinic specializes in treating anal neoplasia, which Berry described as a contentious topic. “I firmly believe that we are preventing anal cancer, but I have to point out that there is absolutely no data that documents identification or eradication of high-grade lesions will actually prevent anal cancer,” Berry said. He said many HGAIN are not palpable and can have negative cytology. In 2002, his office began to use infrared coagulation to treat HGAIN in-office with some success.

It remains to be seen whether HPV vaccination will be found to be a successful prevention for HPV-positive anal cancer and HNSCC, just as it has been for cervical cancer. As studies continue to stratify the level of risk for different patient subgroups, investigators will need to reassess the benefits of HPV vaccination in these populations. Researchers will also need to evaluate whether it is necessary to screen patients with these cancers for HPV and whether HPV-positive disease requires different treatments compared with HPV-negative disease.