Testing a new vaccine to prevent HPV-related cancers in women

Inclusion Criteria:

* Women, age 18 - 60 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 registration
  * 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

Exclusion Criteria:

* History of any of the following:

  * Prior or current genital warts
  * Treatment for anogenital intraepithelial neoplasia (cervical intraepithelial neoplasia \[CIN\], anal intraepithelial neoplasia \[AIN\], vaginal intraepithelial neoplasia \[VAIN\], vulvar intraepithelial neoplasia \[VIN\])
  * Systemic cancer treatment within the prior year
* History of anaphylaxis to vaccines
* 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 or preclude protocol vaccination
* 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 diagnoses:

  * 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)
* Unrecovered major infections and/or surgical procedures