Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase IIIb, Observer-blind Study to Compare Immunogenicity of GSK Biologicals' HPV-16/18 L1/AS04 Vaccine Versus Gardasil® [Quadrivalent Human Papillomavirus (HPV-6,11,16,18 L1 VLP) Recombinant Vaccine Merck & Co., Inc.]
Brief Summary: HPV infection has been established as a necessary cause of cervical cancer. GSK Biologicals has developed an HPV-16/18 L1 VLP AS04 vaccine (Cervarix TM) which targets the 2 most common oncogenic HPV types (HPV-16 and HPV-18), found in \> 70%, approximately, of all cervical cancers. Recently, Merck's HPV vaccine Gardasil® \[quadrivalent human papillomavirus (HPV-6,11,16,18 L1 VLP) recombinant vaccine\] has been approved by the FDA for prevention of genital tract cancers and pre-cancers and genital warts in females. Although the GSK HPV vaccine and Gardasil® have different compositions and are expected to have different efficacy profiles, each vaccine targets prevention of HPV-16 and 18 genital tract cancers and pre-cancers. Therefore, a comparison of the immunogenicity of the two vaccines is warranted. This Phase 3b study is designed to compare the immunogenicity of the GSK vaccine (HPV-16/18) to Gardasil® in healthy adult females 18-45 years of age.

The Protocol Posting has been updated as the study will be extended by 3 additional years.


Options:
A: Inclusion Criteria:

* • Women 18 to 24 years of age who agree to participate by signing an informed consent form prior to recruitment.

  * Girls 9 and 10 years of age whose father/mother/guardian signs the informed consent form to participate in the study.

Exclusion Criteria:

* • Prior administration of an anti-HPV vaccine

  * Pregnant women or women planning to get pregnant in the next 8 months.
  * Auto-immune diseases
  * Women with a history of Guillain Barré syndrome.
  * Prior administration of immunoglobulins and/or any blood product in the past 6 months before the study's first vaccine dose.
B: Inclusion Criteria:

* Subjects who the investigator believes that they can and will comply with the requirements of the protocol;
* Written informed consent obtained from the subject prior to enrolment in the extension study;
* A subject previously vaccinated in the NCT00316693 study.
* Subjects who showed, at the last NCT00316693 study visit (at Month 24) willingness to participate in this extension study.

Exclusion Criteria:

* Use of any HPV vaccine other than the one administered in the NCT00316693 study;
* Use of any investigational or non-registered product other than the study vaccine since last NCT00316693 study visit, or planned use during the study period;
* 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;
* Subjects who were diagnosed high grade or missing cytology at Month 0 in the NCT00316693 study;
* Pregnant females and females who were pregnant less than 3 months ago.
C: Inclusion Criteria:

* A woman whom the investigator believes that she or her legally acceptable representative (in the event that the subject is illiterate) 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 18 and 45 years of age at the time of the first vaccination.
* Written informed consent must be obtained from the subject prior to enrollment.
* Subject must be free of obvious health problems as established by medical history and history-directed clinical examination before entering into the study.
* Subject must have a negative urine pregnancy test.
* Subject must be of non-childbearing potential, or if she is of child bearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
* Subject must have an intact cervix.

Exclusion Criteria:

* 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 up to Month 60.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose or planned administration during the study period up to Month 60.
* 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 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.
* 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 eight months of the study (Months 0-8).
* Previous administration of components of the investigational vaccine
* Previous or planned vaccination against HPV outside of this protocol.
* 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 significant medical conditions and currently under treatment.
* Received immunoglobulins and/or blood product within 90 days preceding enrolment or planned administration during the study period up to Month 60. Enrollment will be deferred until the subject is outside of specified window.
* Acute disease at the time of enrolment. Enrollment will be deferred until condition is resolved. All vaccines can be administered to persons with a minor illness
* 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.
D: Inclusion Criteria:

* Subjects who the investigator believes that they and their parents/legally acceptable representatives can, and will, comply with the requirements of the protocol should be enrolled in the study.
* A female between, and including, 10 and 18 years of age at the time of the first vaccination.
* Written informed consent/assent obtained from the subject prior to enrolment. For subjects above the legal age of consent, written informed consent must be obtained from the subject. For subjects below legal age of consent, written informed consent obtained from the subject's parent/LAR, and written informed assent must be obtained from the subject.
* Healthy subjects, as established by medical history and history-directed physical examination, before entering into the study.
* Previously completed routine childhood vaccinations according to the recommended vaccination schedule at the time.
* Subjects must have a negative urine pregnancy test.
* Subject must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche during the study, and therefore become of childbearing potential, must agree to follow the same precautions.

Exclusion Criteria:

* 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 (up to Month 12/13).
* 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).
* 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 each dose of vaccine(s). Administration of routine vaccines up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
* A woman planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose.
* Pregnant or breastfeeding women.
* Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
* Previous administration of components of the investigational vaccine
* Administration of a diphtheria, tetanus, pertussis (DTP) vaccine, diphtheria-tetanus (Td) booster or dTpa vaccine within the previous five years.
* Administration of a pre-school booster of Oral Polio Vaccine (OPV) or Inactivated Polio Virus (IPV) vaccine (4 or 5th dose) within the previous five years.
* Hypersensitivity to latex.
* Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality or thrombocytopenia, as determined by previous physical examination or laboratory tests.
* Cancer or autoimmune disease under treatment.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
* History of encephalopathy within seven days of administration of a previous dose of pertussis vaccine that is not attributable to another identifiable cause.
* Temperature of \>=40°C within 48 hours of receipt of a prior dose of DTP vaccine (DTPw and/or DTPa), not due to another identifiable cause.
* Collapse or shock-like state within 48 hours of receipt of a prior dose of DTP vaccine (DTPw and/or DTPa).
* Seizures with or without fever within three days of a prior dose of DTP vaccine (Diphtheria, Tetanus, whole cell Pertussis vaccine DTPw and/or Diphtheria, Tetanus, acellular Pertussis vaccine DTPa).
* Persistent, inconsolable crying lasting \>=3 hours, occurring within 48 hours of a prior dose of DTP vaccine (DTPw and/or DTPa).
* Severe Arthus-type hypersensitivity reactions following a prior dose of tetanus toxoid within the previous 10 years.
* Known exposure to diphtheria or household exposure to pertussis within 30 days before (i.e., Day 0-29) vaccination with Diphtheria, Tetanus, acellular Pertussis and inactivated polio virus vaccine (dTpa-IPV).
* Diphtheria and/or tetanus and/or pertussis and/or polio diagnosed within 30 days before (i.e., Day 0-29) vaccination with dTpa-IPV.
* Presence of a contra-indication to vaccination according to the product leaflet of the commercially available dTpa-IPV vaccine.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Acute disease at the time of enrolment.
* Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period. Enrolment will be postponed until the subject is outside the specified window.

Answer: C