Linda Brookes, MSc


October 17, 2013

In This Article

Head and Neck Cancer: A Changing Profile

Editor's Note: The increasing incidence of human papillomavirus (HPV)-positive head and neck cancer prompts questions about management approaches to this evolving disease. At the 2013 European Cancer Congress in Amsterdam, The Netherlands, Dr. Pernille Lassen, researcher from Aarhus University Hospital in Aarhus, Denmark, presented an update on management strategies and then spoke with Linda Brookes, for Medscape, to discuss the clinical implications in greater depth.

The reported prevalence of oropharyngeal carcinomas attributable to HPV varies strikingly by geographical region, with the highest rates in North America and Japan (over 50%) and Europe (approximately 40%), according to the most recent data.[1] However, these figures may be low. Citing the national population-based database maintained by the Danish Head and Neck Cancer Group (DAHANCA), Dr. Pernille Lassen reported a striking 12-fold increase in oropharyngeal cancer between 1977 and 2012, with HPV-positive disease increasing from 37% to 74%. This mirrors what has been seen elsewhere in Europe[2] and in the United States,[3] Dr. Lassen pointed out.

A striking feature of HPV-positive disease is that patients are typically diagnosed with large lymph nodes and so are often in advanced clinical stages at presentation. Nonetheless, they have a better prognosis than HPV-negative patients. As Dr. Lassen explained, "HPV-induced carcinogenesis involves significantly fewer genetic alterations/mutations than carcinogenesis independent of HPV (tobacco), which renders HPV-positive tumors as very receptive to treatment." But an increasing number of patients are being identified with tumors with carcinogenic features from both HPV and tobacco use. "In terms of clinical outcome, these patients fare significantly worse than those with pure HPV-induced tumors and somewhat better than those with HPV-negative (tobacco-induced) carcinomas," Dr. Lassen noted. "These tumors with dual/mixed etiology represent a challenge both in terms of molecular biology and treatment selection," she acknowledged.

HPV Detection

Of the more than 150 different HPV subtypes identified to date, high-risk HPV type 16 represents over 90% of virus isolated in HPV-positive head and neck cancers. In randomized clinical trials of head and neck cancer, tumor HPV/p16 status has been shown to be the strongest independent prognostic factor for tumor control and survival, although this prognostic impact is apparently limited to oropharyngeal cancer. For risk stratification and prognostication, p16 immunohistochemistry (IHC) appears to be useful and easily implementable in daily clinical practice.

"At present we continue to use p16-IHC to detect HPV in head and neck cancer, but we have adapted the system to integrate tumor morphology," Dr. Lassen reported.[4,5] She noted that a Dutch group recently proposed increasing accuracy with a combined algorithm using IHC with p16INK4A immunostaining followed by high-risk HPV general primer 5+/6+ DNA PCR.[6] Comparing it with the gold standard, E6/E7 mRNA detection, the group reported "excellent" performance (100%) in terms of both specificity and sensitivity. They also found that about 5% of tumors were p16-positive but HPV DNA-negative. These patients showed significantly less favorable survival than patients with p16-positive and HPV DNA-positive tumors and might represent overlapping etiology, Dr. Lassen suggested.