Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, International, Double-Blinded (With In-House Blinding), Controlled With GARDASIL, Dose-Ranging, Tolerability, Immunogenicity, and Efficacy Study of a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine Administered to 16- to 26- Year-Old Women
Brief Summary: The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of V503 in comparison to GARDASIL. The primary hypotheses tested in the study were 1) V503 administered to 16- to 26-year-old adolescents and young women is generally well-tolerated, 2) V503 reduces combined incidence of Human Papillomavirus (HPV) Type 31/33/45/52/58-related disease compared with GARDASIL, and 3) V503 induces non-inferior geometric mean titers for HPV Type 6/11/16/18 antibodies compared with GARDASIL.


Options:
A: Inclusion Criteria:

* Subjects who the investigator believes can and will comply with the requirements of the protocol and subjects who the investigator believes their parent(s)/Legally Acceptable Representative(s) (LAR\[s\]) can and will comply with the requirements of the protocol.
* A female between, and including, 9 and 14 years of age at the time of the first vaccination.
* Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to enrolment in the study. In addition, if capable, the subject should sign and personally date a written informed assent.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series.

Exclusion Criteria:

* Pregnant or breastfeeding.
* A woman planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose.
* Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than those foreseen in the protocol.
* Child in care.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 36).
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
* History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccines.
* Cancer or autoimmune disease under treatment.
* Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before each dose of vaccine. Administration of routine meningococcal, hepatitis B, hepatitis A, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* Previous administration of vaccine components.
* Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Family history of congenital or hereditary immunodeficiency.
* Major congenital defects or serious chronic illness.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, which in the opinion of the investigator precludes administration of the study vaccine.
* Acute disease and/or fever at the time of enrolment.
* Drug and/or alcohol abuse.
B: Inclusion Criteria

Children ages ≥ 7 to \< 12 years of age.

A confirmed diagnosis of HIV infection, defined as two positive assays from two different samples. The two results may be in any combination of the following:

* at any age: Deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), Ribonucleic acid (RNA) PCR
* age \> 4 weeks: p24 antigen detection
* age \>18 months: licensed ELISA (Enzyme-linked immunosorbent assay) with confirmatory Western Blot

CD4% ≥ 15 at the time of screening is required (Note that this is a minimum requirement, and that for Stratum C the CD4% needs to be ≥ 25).

For Strata A and B: Currently stable (≥ 3 months) on highly active antiretroviral therapy (HAART) regimen, defined as three or more antiretrovirals from at least two different therapeutic classes, or therapy with the combination of azidothymidine, lamivudine, and abacavir.

For stratum C no antiretroviral therapy is required.

Parent or legal guardian able and willing to provide signed informed consent.

Negative urine pregnancy test sensitive to 25 International Unit (IU) beta-human chorionic gonadotropin (HCG) for girls who are menstruating (child bearing potential).

Female study volunteers who are participating in sexual activity that could lead to pregnancy must agree to use two reliable methods of contraception, one of which must be a barrier method. A barrier method of contraception (condoms or cervical cap) together with another reliable form of contraception (condoms a , with a spermicidal agent; a diaphragm or cervical cap with spermicide; an intrauterine device \[IUD\]; or hormonal-based contraception) must be used while on this study. Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV-1 transmission

Males participating in the study must not attempt to impregnate a woman, or participate in sperm donation programs. Males engaging in sexual activity that could lead to pregnancy must use a condom.

Exclusion Criteria

Body temperature ≥ 101 F or ≥ 38.3 C, orally determined, within 72 hours prior to the first and each subsequent injection. Subjects may be vaccinated any time in the next seven days thereafter, provided that the site investigator is satisfied that the febrile illness has ended.

Total bilirubin ≥ 5 x Upper Limit of Normal (ULN) at screening.

Alanine transaminase (ALT) or serum glutamic pyruvic transaminase (SGPT) ≥ 5 x ULN at screening in the absence of other explained causes (as determined by the site investigator) at screening.

Serum creatinine ≥ 1.5 mg/dL at screening.

Absolute neutrophil count ≤ 750 cells/mm3 at screening.

Hemoglobin ≤ 9.9 g/dL at screening.

Platelet count ≤ 75,000 cells/mm³ at screening.

Presence of an acute opportunistic non-bacterial or bacterial infection requiring therapy at the time of enrollment; the subject may be entered once he/she is stable on appropriate anti-infective therapy.

Chemotherapy for active malignancy.

Other known or suspected disease of the immune system, or immunosuppressive therapy.

Prior treatment with immunosuppressive or immunomodulation therapy within 60 days of screening.

Prior treatment with three or more week-long courses of corticosteroids (≥ 2.0 mg/kg or ≥ 20 mg total of prednisone-equivalent) within one year of screening; or any systemic (oral or parenteral) steroids (≥ 2.0 mg/kg or ≥ 20 mg total of prednisone-equivalent for ≥ 3 days) within 30 days of study entry.

Prior vaccinations with inactivated vaccines received within two weeks of any dose of study vaccine, and no other vaccinations may be planned for two weeks after each dose of study vaccine.

Prior vaccinations with live vaccines received within three weeks before any dose of study vaccine, and no other vaccinations may be planned for two weeks after each dose of study vaccine.

Prior diagnosis of sexually transmitted infections (STIs), genital warts, or juvenile recurrent papillomatosis.

History of any severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention.

Known allergies to any vaccine component, including aluminum, yeast, or BENZONASE™ (nuclease, Nycomed \[used to remove residual nucleic acids from this and other vaccines\]).

Previous treatment with any immune globulin preparation or blood-derived products within the six months prior to the first injection and none may be planned during the study.

Known coagulation disorder that would contraindicate Intramuscular (IM) injections.

Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study.

Breastfeeding.
C: Inclusion Criteria:

* Female between 16- to 26-years-old
* Has never had Pap testing or has only had normal Pap (Papanicolaou) test results
* For the immune memory substudy in the extension (Cohort 1): was randomized to V503 in the base study and was in the per-protocol immunogenicity population for ≥1 HPV type
* For the 3-dose V503 vaccination substudy in the extension (Cohort 2): was randomized to GARDASIL in the base study and received ≥1 dose of GARDASIL

Exclusion Criteria:

* History of an abnormal cervical biopsy result
* History of a positive test for HPV
* History of external genital/vaginal warts
* Currently a user of any illegal drugs or an alcohol abuser
* History of severe allergic reaction that required medical attention
* Are pregnant
* Received marketed HPV vaccine or participated in an HPV trial
* Currently enrolled in a clinical trial
* Currently has or has a history of certain medical conditions or is currently taking or has taken certain medications (details will be discussed at the time of consent.)
D: Inclusion Criteria:

All Participants:

-Judged to be in good physical health on the basis of medical history, physical examination and laboratory results

Boys and Girls 9 to 14 Years:

-Must not have had coitarche and does not plan on becoming sexually active during the vaccination period

Women 16 to 26 Years:

* Has never had a Papanicolaou (Pap) test or only had normal Pap test results
* A lifetime history of 0 to 4 male and/or female sexual partners

Exclusion Criteria:

All Participants:

* Known allergy to any vaccine component
* History of severe allergic reaction that required medical intervention
* Thrombocytopenia or any coagulation disorder
* Females only: participant is pregnant or expecting to donate eggs during day 1 through month 7
* Currently immunocompromised, or been diagnosed with immunodeficiency
* Had a splenectomy
* Receiving or has received immunosuppressive therapies within the last year
* Received any immunoglobulin product or blood-derived product within 3 months
* Received a marketed HPV vaccine or has participated in an HPV vaccine clinical trial

Answer: C