The incidence of HPV related head and neck cancers (HPV+ HNC) is increasing significantly in the United States. At the same time, we are now seeing patients present with, or develop, multiple HPV+ HNCs, which previously was not a clinical scenario that was thought to occur. This year The Faden Lab, along with colleagues at the University of Pittsburgh, Vanderbilt and the National Cancer Institute published the most comprehensive analysis of patients with multiple HPV+ HNCs demonstrating that at least 1-3% of all HPV+HNC patients will have multiple cancers. This number is felt to likely be an underestimation based on the way the data is reported. Because of this finding, the Faden lab, in collaboration with Dr. Jeremy Richmon prospectively evaluated patients at Mass Eye and Ear, finding the rate of multiple primaries is closer to 7.5%. This work is now available in Oral Oncology, here. This clinical scenario presents new and challenging questions related to how these patients should be treated. To better understand why this is occurring, the team then conducted a genomic study analyzing paired tumors from a cohort of patients with multiple HPV+ HNCs showing for the first time that these tumors are caused by the exact same HPV isolate yet possess very different types of DNA and RNA alterations. Further, the tumors develop through different processes and pathways, challenging existing theories on how HPV+HNCs evolve. This work can be found here, in Carcinogenesis.