Testing RG1-VLP Vaccine to Prevent HPV-related Cancers

Eligibility Criteria

• * Women, age 18 - 45 years. Because no dosing or adverse event (AE) data is currently available for the use of RG1-VLP in humans, children and adolescents are excluded from this study
• * White blood cell (WBC) between 3000/mm\^3 - institutional upper limit of normal
• * Hemoglobin (Hgb) between 10 g/dl - institutional upper limit of normal
• * Platelets \>= 100,000/mm\^3
• * Serum creatinine within institutional normal limits
• * Bilirubin =\< 2x institutional upper limit of normal
• * Alanine aminotransferase (ALT) =\< 2x institutional upper limit of normal
• * Aspartate aminotransferase (AST) =\< 2x institutional upper limit of normal
• * Human immunodeficiency virus (HIV)-1/HIV-2 negative
• * Hepatitis B and hepatitis C negative
• * The effects of RG1-VLP vaccination on the developing human fetus at the proposed doses are unknown. For this reason, all women of childbearing potential will have a pregnancy test and all heterosexually active women must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• * The following persons are not considered to be able to bear children and are therefore eligible to participate without the use of concurrent birth control:
• * Female with bilateral oophorectomy and/or hysterectomy
• * Female with fallopian tubes cut, tied or sealed
• * Female with sterilization implant (e.g. Adiana, Essure) placed \> 3 months prior to randomization
• * Female post-menopausal (\> 1 year since last menses or prior laboratory follicle stimulating hormone \[FSH\] value per institutional range indicating post-menopausal)
• * Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• * Ability to understand and the willingness to sign a written informed consent document
• * History of any of the following:
• * Prior or current genital warts
• * For women 25 and older: any abnormal Pap smear and positive HPV deoxyribonucleic acid (DNA) test (if co-testing), or positive HPV DNA test (if primary HPV screening)
• * Treatment for anogenital intraepithelial neoplasia (cervical intraepithelial neoplasia \[CIN\], anal intraepithelial neoplasia \[AIN\], vaginal intraepithelial neoplasia \[VAIN\], vulvar intraepithelial neoplasia \[VIN\])
• * Treatment for any cancer
• * History of anaphylaxis to vaccines or fever \> 100 degrees Fahrenheit (F) within 72 hours of vaccination
• * Any prior vaccination with Gardasil, Gardasil-9, or Cervarix or other HPV vaccine
• * Receipt of blood products within 3 months of enrollment, or continuing plasma donation
• * Participants receiving any other investigational agents
• * History of allergic reactions attributed to compounds of similar chemical or biologic composition to the adjuvant or to RG1-VLP
• * Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
• * Pregnant women or actively lactating women are excluded from this study because RG1-VLP is a vaccine with the potential for teratogenic or abortifacient effects
• * Planned receipt of any inactivated vaccine in the 2 weeks preceding and the 2 weeks following any trial vaccination
• * Planned receipt of any live attenuated vaccine in the 4 weeks preceding and the 4 weeks following any trial vaccination
• * Women with a history of bleeding disorders or use of anticoagulants (aspirin is acceptable)
• * Had prior medical conditions:
• * Rheumatoid arthritis or other auto-immune disease
• * Congenital or acquired immunodeficiency
• * Collagen vascular disease
• * Following medical treatments:
• * Current use of immunosuppressive drugs including corticosteroid use (inhaled or topical steroids are permitted)