HPV-related Oropharyngeal and Uncommon Cancers Screening

PRIMARY OBJECTIVES:

I. To estimate the cumulative 5-year incidence rate of HPV-related malignancies,
oropharyngeal, anal, and penile cancer, in men aged 50-64 who test serologically positive for
antibodies to HPV 16 E antigens.

SECONDARY OBJECTIVES:

I. To evaluate the association of persistent oral HPV deoxyribonucleic acid (DNA) and
subsequent diagnosis of oropharyngeal cancer.

II. To estimate the prevalence of serological antibodies to HPV E antigens in men aged 50-64.

III. To investigate behavioral risk factors for HPV-related malignancies in men.

IV. To compare the incidence rates of HPV-related malignancies, oropharyngeal, anal, and
penile cancer, between the matched HPV serologically positive and negative men.

EXPLORATORY OBJECTIVES:

I. To evaluate the performance of serological testing of HPV, when used for screening men for
HPV-related malignancies.

II. To evaluate the feasibility and performance of narrow band imaging to diagnose
oropharyngeal cancer.

III. To evaluate the feasibility and performance of transcervical ultrasonography of the neck
lymph nodes and oropharynx for early diagnosis of oropharyngeal cancer.

IV. To evaluate the performance of anoscopy and HPV/cytology testing of anal swab (anal
Papanicolaou [Pap]) to diagnose anal cancer.

V. To determine the feasibility of nucleic acid-based techniques (circulating HPV16 DNA
[cvDNA] in serum as well as oral HPV16 DNA and integrated HPV16 DNA in oral rinse and swabs)
to refine high-risk group selection for screening and to facilitate oropharyngeal
localization of cancers and pre-cancers within a group undergoing screening.

VI. To evaluate T cell response to E2, E6, and E7 antigens as a diagnostic biomarker for
HPV-related cancer.

VII. To evaluate the association between oral HPV16 infection and the oral microbiota as well
as factors that modify any such association.

OUTLINE:

STAGE I: Participants undergo collection of blood and oral gargle samples.

STAGE II: Participants complete a head and neck exam by using brushing of the oropharyngeal
mucosa, a thorough oropharyngeal exam including narrow band imaging, undergo collection of
oral gargle sample, transcervical ultrasonography of the neck lymph nodes and oropharynx,
anoscopy, and complete Papanicolaou/HPV testing. Participants undergo repeat oropharyngeal
screening, oral HPV DNA test, oral HPV integration testing, and ultrasound once every 6
months for 5 years. Participants also undergo collection of blood.

Inclusion Criteria:

- Stage 1 Inclusion Criteria: United States (US) resident

- Stage 1 Inclusion Criteria: Fluent in English

- Stage 1 Inclusion Criteria: Sign an approved informed consent document

- Stage 2 (longitudinal study) Inclusion Criteria:

- Eligible for and enrolled in Stage 1

- Test positive to HPV16 E antibodies; be identified as a negative control; test
positive for oral HPV16 infection by oral rinse; or test positive for cvDNA

- Sign an approved informed consent document

Exclusion Criteria:

- Stage 1 Exclusion Criteria: Patients with previously documented squamous cell
carcinoma of the oropharynx, anus, or penis

- Stage 1 Exclusion Criteria: Received radiation cancer therapy to the head and neck in
the past

- Stage 1 Exclusion Criteria: On active cancer therapy now or in the past 6 months

- Stage 1 Exclusion Criteria: Ever had a transplant (stem cell, bone marrow, or solid
organ)

- Stage 1 Exclusion Criteria: Patients who received blood transfusions in the last 6
months

- Stage 1 Exclusion Criteria: Other medical or psychiatric illness or social situation
that would limit study compliance

- Stage 2 (longitudinal study) Exclusion Criteria: Any seronegative and cvDNA-negative
man who tests negative for oral HPV16 DNA by swab at two consecutive follow-up visits
will be excluded from further follow-up. Any man who is seropositive, cvDNA-positive,
or has evidence of integration at any time will continue to be followed regardless of
oral HPV16 status