Human papillomavirus (HPV) is the cause of cervical cancer, as well as subsets of cancers at other anatomic sites, including the oropharynx, vulva/vagina, penis, and anus. There have also been purported associations between HPV and cancers at other anatomic sites in the head and neck from case-series and case-control studies; only one study has prospectively linked HPV with a subset of head and neck cancers (HNC). Since that time there have been numerous advances in HPV technology, and many new assays are available. Therefore, we aim to prospectively evaluate the risk conferred by HPV serostatus detected prior to diagnosis of cancers at multiple anatomic sites in the head and neck.