Barbara Burtness, MD, Chief, head and neck medical oncology, co-leader, developmental therapeutics, Fox Chase Cancer Center, compares the biological differences between advanced head and neck cancers that are derived from traditional factors and those from the human papillomavirus (HPV).

Traditional head and neck cancer is closely associated with exposure to tobacco and alcohol. The biology of this type of cancer is well understood and generally contains a mutation in p53, heterozygosity in p16, and carries a high mutation burden. This type of cancer is generally very resistant to therapy.

Head and neck cancers that are caused by HPV infection develop primarily in the oropharynx. There are many different strains of HPV with several high-risk cancer causing variations; HPV-16 is the most common form in the US. HPV-16 related cancer does not generally develop a p53 mutation, which makes this type less resistant to chemotherapy. The expression of viral oncoproteins leads to the degradation of both p53 and Rb proteins, which causes a compensatory upregulation of p16. The overall low mutational burden in HPV-positive head and neck cancers results in a higher treatment response than HPV-negative types.

Burtness describes 2 large studies that evaluated the effects of intensifying therapy in advanced head and neck cancer. The first was the TROG 02.02 that looked at the impact of radiotherapy quality on outcomes and the second was the RTOG 0129 that examined the effects of radiation and cisplatin intensity. These trials demonstrated that therapy intensity and quality did not significantly improve cure rates, however subset analyses within these trials did find that HPV status effected outcomes significantly. Patients that were HPV-positive experienced 80-85% better outcomes, compared to those that were HPV-negative.