This is a phase 2, open-label study to assess the immunogenicity of the 9-valent human papillomavirus (HPV) recombinant vaccine (Gardasil9) in people born male with current or past exposure to androgen blockers or estrogen (BM-EABE). Investigators will enroll BM-EABE with HIV and HIV negative controls (BM-EABE or men who have sex with a person with a penis (MSPP)) and administer Gardasil9 at timepoints Day 0, Month 2, and Month 6. The immune response to the vaccine will be analyzed at Month 7 (1 month following the final vaccine dose).

This will be a phase 2, open-label study to assess the humoral and cellular immune response to the FDA-approved 9-valent HPV recombinant vaccine in people born male with current or past exposure to androgen blockers or estrogen (BM-EABE). At baseline, BM-EABE with HIV, HIV negative controls (BM-EABE or men who have sex with a person with a penis (MSPP)) will provide blood samples and anal swabs for evaluation of HPV immunity, anal HPV and anal dysplasia. All participants will undergo a 3-dose vaccine series of the Gardasil vaccine (at Day 0, Month 2 and Month 6). Participants will then return one month after completion of third vaccine (Month 7) to provide repeat blood samples and anal swabs. Samples will be compared pre and post vaccination and in-between participants based on HIV and exposure to androgen blockers or estrogen (EABE).

Any participant with human papillomavirus 16 (HPV16) and/or anal dysplasia on anal cytology at any point will be referred to high-resolution anoscopy (HRA) for clinical management. Anal biopsies will be procured from different pathology laboratories - after clinical evaluation has been complete - for research analysis, including confocal microscopy. Those who had anal dysplasia at study entry will undergo repeat HRA, as clinically indicated, and will have an optional study visit following their repeat HRA to provide blood draw and anal swabs.

Inclusion Criteria:

• 18 years old or older and 70 years old or younger
• Able to provide informed consent
• Denies history of prior HPV vaccination with Gardasil9 (receipt of HPV vaccination other than Gardasil9 such as the bivalent or the quadrivalent HPV vaccine will be allowed) or unsure of vaccination status and born before 2003
• Born Male

For Test group: HIV-positive people born male with current or past exposure to androgen blockers or estrogen (BM-EABE)

• Living with HIV
• Current or past exposure to androgen blockers or estradiol

For Control group: HIV-negative Control

• HIV negative
• Either: Current or past exposure to androgen blockers or estradiol; no current or past exposure to androgen blockers or estradiol AND had sex with a person with a penis in the last year

Exclusion Criteria:

• Younger than 18 years old or older than 70 years old.
• Self-reported or documented history of nine-valent HPV vaccine or unsure of vaccination status and born after 2003.
• Born female
• History of hypersensitivity, including severe reactions to yeast or other component of the vaccine.
• Any condition requiring systemic chemotherapy or immunomodulant affecting antibody responses (i.e., rituximab, ibrutinib etc.), intravenous or subcutaneous immunoglobulin supplementation, radiation therapy, or immunomodulatory treatment within the previous 6 months (presence of precancerous lesions is not exclusionary).

The principal investigator will share de-identified data with approved researchers at the time of publication or shortly afterwards.

Data will be made available at the time of publication or shortly following publication, and will be available indefinitely.

The criteria will be determined by the Principal Investigator