This study will screen people for oncogenic oral Human Papillomavirus (HPV) infection and antibodies to form a cohort of people who may be at increased risk of HPV-oropharyngeal cancer (HPV-OPC). The investigators will follow these individuals prospectively to evaluate oncogenic oral HPV persistence, risk factors, and biomarkers for persistence.

This study will provide one of the first estimates of long-term oral HPV natural history, and the effect of biologic and behavioral risk factors, including HIV, on this natural history. Phase 1 of the study will screen approximately 1500 people for oncogenic oral HPV biomarkers. Phase 2 of the study will follow only those subjects with oncogenic oral HPV infection and/or HPV serum oncogene antibodies from Phase 1 (and those previously identified as having oncogenic oral HPV infection in a previous study) with annual follow-up for oncogenic oral HPV persistence.

Understanding persistent oncogenic oral HPV infection is the focus of this study. Understanding which factors drive oral HPV infection to become persistent or progress to malignancy is critical to determine who is at high risk for oropharyngeal cancer and may benefit from screening and prevention. It is presumed that persistent oncogenic oral HPV infections are necessary for progression to HPV-OPC.

The study is led by Dr. Amber D'Souza and Dr Carole Fakhry (Johns Hopkins) and participants are being enrolled in Baltimore MD (Johns Hopkins) and in New York (Mt. Sinai).

Participants in the Phase 1 Screening

Inclusion criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• 18 and older (enrollment at most sites will be restricted to 30 and older since this demographic has the highest prevalence of infection; however, individuals and/or partners of someone with an HPV-related cancer, for example, are at increased risk so will be enrolled in the larger age range).
• Willing to be contacted to arrange follow-up visits, if determined to be eligible for phase 2
• Ability to understand and the willingness to sign a written informed consent document

In addition, individuals must meet at least one of the following criteria:

• Male, aged 30 and older, with 2 or more lifetime oral sex
• History of anal or genital dysplasia or cancer
• Partners of someone with an HPV-related cancer (HPV-positive OPC, anal cancer or genital cancer)
• Known oncogenic HPV-positive biomarker from prior studies or testing, regardless of number of partners.

Exclusion criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Presence of medical or psychiatric condition affecting ability to give voluntary, informed consent.
• Participants who do not speak English cannot enroll because the consent and study survey are only available in English. However, if there is a hearing, literacy or minor fluency issue and the participant requests assistance from a family member or the study coordinator, this individual may still enroll and receive this assistance to ensure they fully hear and understand everything being asked.
• History of head and neck cancer

Participants in the Phase 2 Follow-Up

Inclusion criteria:

• Oncogenic oral HPV infection and/or HPV serum oncogenic antibodies detected in phase 1
• Willingness to complete annual follow up visits

Exclusion criteria:

• Unable to complete annual follow up visits

Target sample size: 1325 (phase 1), ~250 (phase 2) Inclusion of women and minorities: Primary enrollment is restricted to men, given their higher risk of infection (see eligibility criteria). However, the investigators expect to enroll women with cervical dysplasia and partners of patients with HPV-related cancer (~125 expected women enrollees). Enrollment is across many different sources (geographically, and by clinic type), and is inclusive of diverse racial and ethnic backgrounds. Enrollment is not stratified by race but the investigators expect to enroll at least 175 minorities in the study.