HPV in Tumors Predicts Survival from Throat Cancer
By Kie Kian Ang, MD, PhD
It is now known that the prevalence of HPV-related throat cancer is increasing in the United States and other Western countries. This rise in incidence is due to changing sexual behavior. Patients with HPV-related throat cancer have on average a higher number of sex partners, particularly the number of oral sex partners.
According to our recent study published in The New England Journal of Medicine, the presence of human papilloma virus (HPV), which is known to cause cervical cancer in women, appears to be the best indicator of whether those diagnosed with oropharyngeal cancer will survive. Our team of researchers analyzed tumors of those with Stage III or Stage IV oropharyngeal cancer, with results demonstrating that the presence of HPV in tumors coincided with a better response to traditional cancer therapies than other factors, such as age or tumor size. Smoking history was the second leading predictor of survival.
This study has established firmly that HPV-related throat cancer (oropharyngeal carcinoma) differs from smoking-induced head-and-neck cancers in many ways. For example, the majority of patients with HPV-positive throat carcinoma are middle-aged white men, have higher socioeconomic status, consume no or a relatively low quantity of tobacco and/or alcohol, and have slightly smaller tumors at the time of diagnosis. On a positive note, HPV-positive cancer responds much better to currently available therapy modalities, such as radiation combined with chemotherapy. Consequently, the majority of these patients are cured of their cancer.
Research is currently ongoing to find effective, less toxic treatment for this distinct cancer entity to improve the quality of life of cancer survivors. Several clinical trials specifically designed for patients with HPV-related throat cancer have recently been started or will soon begin to enroll patients. The trial of Radiation Therapy Oncology Group (RTOG 1016) is such an example. The RTOG website, www.rtog.org, has more information about this trial. We are hopeful that combining an individual’s HPV status, smoking history, and stage of cancer could potentially help determine how aggressive their therapy should be.
Of note, however, is that while the vast majority of sexually active people have been exposed to HPV infection, which is ubiquitous, only relatively few individuals develop throat cancer. What makes some people more likely to develop HPV-related throat cancer than others is not well understood and is a subject for investigations.
The role and cost-benefit of HPV vaccine in preventing throat cancer is being discussed. It should be kept in mind that HPV vaccine can also prevent some cancers and annoying warts occurring at the anal-genital regions. To be effective, however, vaccination must be given before boys and girls become sexually active.
Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML
Featured in The New England Journal of Medicine.
2010;363(1):24-35. Epub 2010 Jun 7.
Background: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.
Methods: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer.
Results: The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage.
Conclusions: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.)
About the Author
Kie Kian Ang, MD, PhD
Professor and Gilbert H. Fletcher
Distinguished Memorial Chair
Department of Radiation Oncology
Division of Radiation Oncology
The University of Texas
MD Anderson Cancer Center