Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Double-blind, Randomized, Controlled, Multi-center Study to Evaluate the Efficacy of GlaxoSmithKline Biologicals. HPV-16/18 VLP AS04 Vaccine Compared to Hepatitis A Vaccine as Control in Prevention of Persistent HPV-16 or HPV-18 Cervical Infection and Cervical Neoplasia, Administered Intramuscularly According to a 0, 1, 6 Month Schedule in Healthy Females 15-25 Years of Age.
Brief Summary: Human Papilloma virus (HPV) are viruses that cause a common infection of the skin and genitals in men and women. Several types of HPV infection are transmitted by sexual activity and, in women, can infect the cervix (part of the uterus or womb). This infection often goes away by itself, but if it does not go away (this is called persistent infection), it can lead in women over a long period of time to cancer of the cervix. If a woman is not infected by HPV, it is very unlikely that she will get cervical cancer. This study will evaluate the efficacy of GSK Biologicals HPV 16/18 VLP/AS04 vaccine to prevent infection associated cervical pre-cancer and vaccine with HPV 16 or 18 and the vaccine safety, over 48 months, in young adolescents and women of 15/25 years of age at study start. Approximately 18.000 study subjects will either receive the HPV vaccine or a control vaccine (hepatitis A vaccine) administered intramuscularly according to a 0-1-6 month schedule.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Options:
A: Inclusion Criteria:

* The subject has had a documented colonoscopy to the cecum performed by a study-related physician with adequate preparation resulting in diagnosis and clearance of an adenomatous polyp(s) within 4 months prior to randomization.
* The subject is willing to abstain from chronic use of all NSAIDs or COX-2 inhibitors excluding aspirin at cardioprotective doses for the duration of the study.

Exclusion Criteria:

* The subject has a history of Familial Adenomatous Polyposis or Hereditary Non-Polyposis Colorectal Cancer.
* The subject has a history of inflammatory bowel disease.
B: Inclusion Criteria:

* The subject has had a documented colonoscopy to the cecum, by a study physician, with adequate preparation resulting in diagnosis and clearance of an adenomatous polyp(s) within 24 weeks prior to study entry; the 24- week period begins from the time of colonoscopy, which had resulted in full visualization of colon/rectum or the time of removal of adenoma which ever had occurred first
* At the baseline colonoscopy, the subject must have one of the following documented:

  * One adenomatous polyp \> 6 mm;

    * If the colonoscopy report says that a 6 mm polyp was removed, and the local pathology report confirms that this adenoma was AT LEAST 6mm in any dimension, the subject is eligible
    * If the colonoscopy report says that the 6mm polyp was removed, and the local pathology report says that multiple fragments of adenoma were obtained, the subject is eligible
    * If the colonoscopy report says that a 6mm polyp was removed, but the pathologist measured this as 5mm or less in greatest dimension, the subject is NOT eligible
  * Two or more adenomatous polyps of any size documented by local pathology report plus colonoscopy report; or
  * One adenomatous polyp of any size and a documented history of adenomatous polyp(s); if the colonoscopy report indicates that polyps of any size were left in the subject, the subject is NOT eligible; if the colonoscopy report says that all visible adenomas were removed, the subject is eligible.

If the colonoscopy report does not specifically state that all visible adenomas were removed, but does not describe any adenomas that were left in, the subject is eligible

* The subject is willing to abstain from chronic use of all NSAIDs or COX-2 inhibitors, excluding aspirin (cardioprotective doses of less than or equal to 325mg po QOD or 162.5mg po QD) for the duration of the study; chronic use of NSAIDs is defined as a frequency 1 week (7 consecutive days) for more than three weeks per year
* The subject is willing to limit aspirin use to less than or equal to 325mg po QOD or 162.5mg po QD for the duration of the study
* The subset of subjects undergoing SEB analysis will be required to abstain from any aspirin use for the duration of the study
* The subjects' anticipated use of oral/intravenous corticosteroid must be less than 2 weeks over a 6 month period
* The subject's anticipated use of orally inhaled steroid must be less than 4 weeks over a 6 month period; if nasally inhaled steroid use is anticipated, the subject agrees to use mometasone (Nasonex) only. Use of mometasone is not restricted (all other nasal steroids are prohibited); subjects may change to mometasone, but must have discontinued the previous nasal steroid for at least 30 days prior to randomization
* If a subject is female and of child-bearing potential (women are considered not of childbearing potential if they are at least 2 years post-menopausal and/or surgically sterile), she:

  * Has been using adequate contraception (abstinence, IUD, birth control pills, or spermicidal gel with diaphragm or condom) since her last menses and will use adequate contraception during the study,
  * Is not lactating, and
  * Has a documented negative serum or negative urine pregnancy tests within 14 days prior to study entry
* The subject must sign and date the informed consent statement
* Hemoglobin level of greater than 11.5 (both men and women)
* WBC count greater than 3000/mm\^3
* Platelet count greater than 125,000
* Creatinine =\< 1.5 X ULN
* AST =\< 1.5 X ULN
* ALT =\< 1.5 X ULN
* Total bilirubin =\< 1.5 X ULN, unless the subject has Gilbert's disease, for which total bilirubin must be =\< 2.0 X ULN
* Inclusion Criteria for the 2-year post-treatment safety assessment:

  * Subjects who were enrolled in the Year-3 study will be eligible for a 2-year post-treatment safety assessment
  * Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 2-year post-treatment safety assessment:

    * Have been enrolled on the 3-year randomized portion of the clinical trial
    * Willingness to continue with follow-up annual contacts for safety data collection
    * The subject has signed and dated an addendum (Subject Letter) to the informed consent document prior to performing any post-treatment safety assessment procedures
* Inclusion Criteria for Post-treatment Follow-up Colonoscopy:

  * All Subjects who completed Year 3 colonoscopy will be eligible for a post-treatment follow up colonoscopy 2 years after Year 3 colonoscopy
  * Subjects must meet all of the following inclusion criteria to be eligible for follow up colonoscopy:

    * Completion of study treatment (3 years of study drug or on study drug on December 17, 2004) on the 3-year randomized portion of the clinical trial
    * Willingness to continue with follow-up contacts every 6 months for collecting concomitant medications use data and end-of-study colonoscopy at Year 5
    * The subject has signed and dated a separate informed consent document prior to performing any follow-up procedures; while delay in obtaining consent is not optimal, patients may be consented and entered into the post-treatment follow-up study at any time prior to their Year 5 colonoscopy but no later than 1Q2007

Exclusion Criteria:

* The subject has a history of Familial Adenomatous Polyposis or Hereditary Non-Polyposis Colorectal Cancer (as defined by the Amsterdam Criteria)
* The subject has a history of inflammatory bowel disease
* Subject has a chronic or acute renal or hepatic disorder or a significant bleeding disorder
* The subject has a history of hypersensitivity to COX-2 inhibitors, NSAIDs, salicylates, or sulfonamides
* The subject has a history of large bowel resection, except appendectomy
* The subject has used NSAIDs, excluding aspirin at any dose at a frequency equal to or greater than three times per week during the two months prior to randomization
* The subject used aspirin at a dose exceeding 325mg QOD or 162.5mg QD at a frequency equal to or greater than three times per week during the two months prior to study entry
* For SEB measurement participants only: the subject used any dose of aspirin at a frequency greater than once weekly during the two months prior to study entry
* The subject used oral/intravenous corticosteroids for more than 2 weeks in past 6 months
* The subject used orally inhaled corticosteroids for more than 4 weeks in past 6 months and/or the subject has used nasally inhaled corticosteroids (except mometasone) within the last month prior to randomization
* The subject has treatment for a gastrointestinal ulcer in the past month prior to study entry
* The subject has a history of invasive cancer within the past five years (excluding non-melanoma skin cancer)
* The subject has received any investigational medication within 30 days prior to randomization or is scheduled to receive an investigational drug other than celecoxib during the course of the study
* The subject is unable to return for follow-up tests
* The subject participated in the study previously and had been withdrawn
* Subjects whom, in the opinion of the Lead PI, Institutional PI, or Subinvestigator are not appropriate candidates for Study participation
* Subjects currently using triazole or azole antifungal agents (i.e., fluconazole) or lithium
C: Inclusion Criteria:

* Patients must have histologically proven CIN 2/3 or CIN 3 diagnosed by cervical biopsy between 2 and 8 weeks prior to enrollment

  * For a patient to be eligible, the pathology report must clearly state "CIN 2/3" or "CIN 3" or must state "moderate-severe dysplasia", "moderate-severe dyskaryosis," "severe dysplasia," or "severe dyskaryosis;" patients with a diagnosis of CIN 2 alone or moderate dysplasia or dyskaryosis alone are not eligible for this study (3/26/2007)
* Patients must have a satisfactory (readable, good quality) colposcopic evaluation at least 14 days after diagnostic biopsy
* Patients must have signed an approved informed consent and authorization permitting release of personal health information
* Patients must have colposcopically visible cervical lesion at entry consistent with biopsy
* Patients must have a negative urine pregnancy test; women of childbearing potential must practice an acceptable form of contraception (e.g. intrauterine device, contraceptive pills, diaphragm, condoms)
* Patients must have a GOG Performance Status of 0, 1, or 2
* Patients must agree to refrain from using non-steroidal anti-inflammatory drugs (NSAIDS) and aspirin during the time they are taking the study medication
* Patients must be good candidates for delayed treatment of their CIN, i.e. they must be reliable to return for follow-up and provide a combination of at least three phone numbers or addresses for contact
* Hemoglobin (HgB) greater than 11.0g/dl
* White blood cell (WBC) count greater than 3000/mcl
* Platelet count greater than 125,000/mcl (3/26/2007)
* Creatinine less than or equal to 1.5 x upper limit normal (ULN)
* Total bilirubin less than or equal to 1.5 x ULN excluding Gilbert's disease
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.0 x ULN

Exclusion Criteria:

* Patients who are pregnant or lactating
* Patients with cytologic or biopsy evidence of endocervical dysplasia or invasive cancer
* Patients with undiagnosed abnormal vaginal bleeding
* Patients who have previously taken celecoxib or any other COX-2 inhibitor at a frequency of greater than 3 times per week within 2 months (60 days) prior to randomization; patients can use Naproxen without restriction (6/23/2008)
* Patients with a known immunocompromised condition
* Patients who have had a known allergic reaction to any NSAIDS or aspirin (asthma, urticaria, allergic-type reaction)
* Patients with a prior history of cervical cancer
* Patients with hypersensitivity to Celecoxib
* Patients with a known allergic reaction to sulfonamides
* Patients with a history of peptic ulcer disease
* Patients currently using fluconazole or lithium
* Patients with a chronic or acute renal, or hepatic disorder, a significant bleeding disorder, or any other condition which in the investigator's opinion might preclude study participation for the duration of the trial
* Patients with a history of transient ischemic attack (TIA), stroke, cardiovascular disease or uncontrolled hypertension
D: Inclusion Criteria:

* A woman whom the investigator believes that she and/or her parents/legally acceptable representative can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
* A woman between, and including, 15 and 25 years of age at the time of the first vaccination.
* Written informed consent must be obtained from the subject prior to enrollment (for subjects below the legal age of consent, written informed consent must be obtained from a parent or legal guardian of the subject and, in addition, the subject should sign and personally date a written informed assent).
* Subject must be free of obvious health problems as established by medical history and clinical examination before entering into the study.
* Subject must have a negative urine pregnancy test.
* Subject must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or must be using adequate contraceptive precautions for 30 days prior to the first vaccination and must agree to continue such precautions for two months after completion of the vaccination series.
* Has had no more than 6 lifetime sexual partners prior to enrollment. This criterion may not be applicable in subjects less than 18 years of age, according to local regulatory/ethical requirements.
* Subject must have intact cervix.

Exclusion Criteria:

* Pregnant or breastfeeding. Women must be at least 3 months post-pregnancy and not breastfeeding to enter the study.
* A woman planning to become pregnant or planning to discontinue contraceptive precautions during approximately the first nine months of the study (Months 0-8).
* Previous administration of components of the investigational vaccine.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
* Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after (i.e. days 0-29) each dose of vaccine. Administration of some routine vaccines up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
* Previous vaccination against human papillomavirus (HPV).
* History of vaccination against Hepatitis A or a known clinical history of Hepatitis A disease.
* History of having had colposcopy or has planned a colposcopy to evaluate an abnormal cervical cytology (Pap smear) test.
* Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination.
* History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccines.
* Hypersensitivity to latex.
* Known acute or chronic, clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
* History of chronic condition(s) requiring treatment.
* Received immunoglobulins and/or blood product within 90 days preceding enrollment. Enrollment will be deferred until the subject is outside of specified window.
* Acute disease at the time of enrolment.
* Heavy bleeding (menstruation or other) or heavy vaginal discharge in which a pelvic exam cannot be performed. Enrollment will be deferred until condition is resolved according to investigator's medical judgement.

Answer: D