New Connection Studied Between Oropharyngeal Cancer and HPV
Incidence rates for overall oropharyngeal cancer, human papillomavirus (HPV)–positive oropharyngeal cancers, and HPV-negative oropharyngeal cancers during 1988 to 2004 in Hawaii, Iowa, and Los Angeles. Incidence rates for HPV-positive oropharyngeal cancers increased from 0.8 per 100,000 during 1988 to 1990 to 2.6 per 100,000 during 2003 to 2004. Incidence rates for HPV-negative oropharyngeal cancers significantly declined from 2.0 per 100,000 during 1988 to 2004 to 1.0 per 100,000 during 2003 to 2004. Overall incidence of oropharyngeal cancers increased from 2.8 per 100,000 during 1988 to 1990 to 3.6 per 100,000 during 2003 to 2004.5 Reprinted with permission. © 2011 American Society of Clinical Oncology. All rights reserved.
For decades, oropharyngeal carcinoma has been associated with patient behaviors such as smoking and drinking, but in recent years, scientists have recognized another cause of the disease, the human papillomavirus (HPV). The incidence of these types of oropharyngeal cancer has been dramatically increasing, according to a recent study.1 In fact, the Centers for Disease Control and Prevention (CDC) now reports that 72% of oropharyngeal cancer cases are related to HPV.2 Collaborative care and the use of newer treatment options, both medical and surgical, can yield significant benefits to the patient.
Patients with oropharynx cancers tend to have better outcomes, particularly at high-volume centers, according to many studies.3 “We probably see over 500 new head and neck cancer patients per year,” says Jonathan Mark, MD, Assistant Professor of Head and Neck Surgery at the University of Cincinnati Medical Center. Maintaining patient quality of life during cancer treatment is paramount, and the reason many departments at UC Medical Center unite for a weekly multidisciplinary tumor board to discuss each case and develop the optimal treatment plan for each patient. Team members include a head and neck surgeon, a medical oncologist, a radiation oncologist, a neuroradiologist, oncology nurses, and other allied medical personnel.
Mark confirms that patients with HPV-associated oropharyngeal cancers tend to be younger and healthier in general, which has led to efforts to de-escalate their treatment to avoid serious side effects and improve their long-term quality of life, while maintaining treatment efficacy.1 One way to de-escalate treatment may be to prepare patients for later chemotherapy treatment with a course of the oral diabetes medication metformin. Metformin appears to interfere directly with cell proliferation and apoptosis in cancer cells in a non-insulin-mediated manner.4 One of the key mechanisms of this medication is the activation of adenosine monophosphate activated protein kinase (AMPK).3 Therefore, simultaneously targeting AMPK through metformin and the PI3K/AKT/mTOR cellular signaling pathway in cancer by an mTOR inhibitor could become a therapeutic approach.3 UC Medical Center is conducting clinical trials for many treatment combinations, and one of the most important is the “Dose-finding Study of Metformin with Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma,” which is currently recruiting participants. While de-escalation of therapy is not a proven approach yet, it is a promising one.
Mark emphasizes that the most important step is identifying HPV tumors that may have metastasized during an “unknown primary workup.” These tumors, often found in the oropharynx, can be recognized by using special histological stains. Using transoral robotic techniques, surgeons can then remove the tumor tissue, providing a vastly more targeted course of radiation therapy. This surgical approach accompanies more moderate medical treatment regimens to maintain quality of life in this group of oropharyngeal cancer patients.
References: 1. Boscolo-Rizzo P, Pawlita M, Holzinger D. From HPV-positive towards HPV-driven oropharyngeal squamous cell carcinomas. Cancer Treat Rev. 2015 Oct 31. pii: S0305-7372(15)00194-2. 2. http://www.cdc.gov/cancer/hpv/statistics/headneck.htm. Accessed November 9, 2015. 3. Gourin CG, Forastiere AA, Sanguineti G, Marur S, Koch WM and Bristow RE. Impact of Surgeon and Hospital Volume on Short-Term Outcomes and Cost of Oropharyngeal Cancer Surgical Care. Laryngoscope. 2011 Apr; 121(4): 746–752. 4. Liu H, Scholz C, Zang C, Schefe JH, Habbel P, Regierer AC, et al. Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer cells to the cytotoxic effect of chemotherapeutic drugs in vitro. Anticancer Res. 2012 May;32(5):1627-37. 5. Chaturvedi, K. et al: J Clin Oncol 29(32), 2011: 4294-4301.
Jonathan Mark, MD
Assistant Professor of Head and Neck Surgery
Phone: (630) 650-3403
Email: markjr@ucmail.uc.edu
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