HPV Vaccine Therapy in Interrupting Progression in Patients With High-Grade Vulvar or Anal Lesions

PRIMARY OBJECTIVES:

I. Test if the recombinant human papillomavirus nonavalent vaccine (9vHPV vaccine) delivered
after treatment for high grade squamous intraepithelial lesion (HSIL) reduces the risk of
histologically confirmed recurrent neoplastic lesions (HSIL) by 50% in the vaccinated versus
(vs.) placebo arms.

II. Evaluate safety of the HPV vaccine in HSIL participants.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive recombinant human papillomavirus nonavalent vaccine intramuscularly
(IM) at baseline, 2 months, and 6 months.

ARM II: Patients receive placebo IM at baseline, 2 months, and 6 months.

After completion of study treatment, patients are followed up at months 7, 12, 18, 24, 36,
and 42.

Inclusion Criteria:

- Age 27- 69 at enrollment

- Histologically confirmed diagnosis of initial or recurrent anal or vulvar high-grade
squamous intraepithelial lesion diagnosed on or after 1/1/2014; study pathologist will
use p16 staining as needed to rule out low-grade squamous intraepithelial lesion
(LSIL) disease

- >= 2 months since last therapy for HSIL

- No clinical evidence of HSIL on screening examination; if HSIL is suspected, a biopsy
will be done to exclude HSIL; patients whose screening visit reveals HSIL on biopsy,
may be re-screened one time, >= 2 months after therapy

- Resident in the area and willing to attend up to 7 clinic visits for a 36-month period
at the Virology Research Clinic (VRC)

- Sexually active women of child-bearing potential must be willing to use effective
contraception through month 7 of the study

- If HIV positive, receipt of anti-retroviral therapy continuously for at least 6 months
prior to enrollment

- Ability to give informed consent

- Willingness to sign medical records release form and tissue release form

Exclusion Criteria:

- Currently pregnant

- Chemotherapy (current, within the last month, or anticipated in the next 7 months)

- Prior history of invasive HPV-related anogenital cancer (cervical, vaginal, vulvar,
penile, or anal cancer), or oropharyngeal cancer (base of tongue, tonsil); prior
cancer at other sites (including most of oral cavity) or larynx are not exclusions

- Unstable medical condition (e.g., another malignancy requiring treatment, malignant
hypertension, poorly controlled diabetes, another cancer except for fully excised
non-melanoma skin cancer)

- Prior HPV vaccination

- Known allergy or intolerance to lidocaine

- Currently participating in an interventional research study related to HPV, except the
Anal Cancer HSIL Outcomes Research (ANCHOR) study (NCT02135419)

- Any other condition which, in the opinion of the investigator, may compromise the
subject's ability to follow study procedures and safely complete the study