Gynaecological Follow-up of a Subset of 580299/008 (NCT00122681) Study Subjects

Primary outcomes

1. Number of Subjects With HPV DNA in Cervical Samples by Hybrid Capture 2 Test (HCII)

   Time frame: At Months 12, 24, 36, 48

   Subjects who presented oncogenic HPV DNA in cervical samples by HPV DNA testing. The presence of oncogenic HPV infection was determined by the Hybrid Capture 2 (HCII) test, which detects HPV DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68.

   Missing = For some of the subjects whose result was indicated as quantity not sufficient (QNS).

2. Number of Subjects With Colposcopy Referral and Colposcopy Adequacy

   Time frame: At Months 12, 24, 36, 48

   Subjects with normal cervical cytology, who were found to be oncogenic HPV DNA positive in two subsequent tests, were referred to colposcopy. The result of the subjects' last HPV-008 study visit was taken into account at Visit 1. Subjects with a single cervical cytology reading of ≥ atypical squamous cells of undetermined significance (ASC-US) positive for oncogenic HPV DNA were referred for colposcopy. Subjects with a single cervical cytology reading of ≥ low grade squamous intraepithelial lesion (LSIL) were referred to colposcopy, irrespective of their oncogenic HPV DNA test result.

3. Number of Subjects With Cytological Abnormalities in Cervical Samples by ThinPrep PapTest

   Time frame: At Months 12, 24, 36, 48

   Subjects who presented normal, ASC-US (Atypical Squamous Cell of Undetermined Significance), LSIL (Low-grade Squamous Intraepithelial Lesions), HSIL (High-grade Squamous Intraepithelial Lesions), AGC (Atypical Glandular Cells), ASC-H (Atypical Squamous Cells cannot exclude HSIL) cervical cytology.

   Cervical cytology examination was performed using the ThinPrep PapTest. Note: One subject may have presented with different cytology results at the yearly visit throughout the maximum 4-year follow-up period and therefore may be counted in more than one result category in the analysis.

4. Number of Subjects With Cervical Biopsy Results at Month 12

   Time frame: At Month 12

   Subjects with negative and positive cervical biopsy results for only CIN1, only CIN2, only CIN3, CIN1 and CIN2, CIN1 and CIN3, CIN2 and CIN3, CIN1 and CIN2 and CIN3, AIS, Invasive malignancy, other.

   CIN = Cervical intraepithelial neoplasia. CIN1/CIN2/CIN3 = Cervical intraepithelial neoplasia grade 1/grade 2/grade 3.

   Note: Only CIN1/Only CIN2/Only CIN3 categories contain the subject who has only CIN1/CIN2/CIN3, but not the combinations.

5. Number of Subjects With Cervical Biopsy Results at Month 24

   Time frame: At Month 24

   Subjects with negative and positive cervical biopsy results for only CIN1, only CIN2, only CIN3, CIN1 and CIN2, CIN1 and CIN3, CIN2 and CIN3, CIN1 and CIN2 and CIN3, AIS, Invasive malignancy, other.

   CIN = Cervical intraepithelial neoplasia. CIN1/CIN2/CIN3 = Cervical intraepithelial neoplasia grade 1/grade 2/grade 3.

   Note: Only CIN1/Only CIN2/Only CIN3 categories contain the subject who has only CIN1/CIN2/CIN3, but not the combinations.

6. Number of Subjects With Cervical Biopsy Results at Month 36

   Time frame: At Month 36

   Subjects with negative and positive cervical biopsy results for only CIN1, only CIN2, only CIN3, CIN1 and CIN2, CIN1 and CIN3, CIN2 and CIN3, CIN1 and CIN2 and CIN3, AIS, Invasive malignancy, other.

   CIN = Cervical intraepithelial neoplasia. CIN1/CIN2/CIN3 = Cervical intraepithelial neoplasia grade 1/grade 2/grade 3.

   Note: Only CIN1/Only CIN2/Only CIN3 categories contain the subject who has only CIN1/CIN2/CIN3, but not the combinations.

7. Number of Subjects With Cervical Biopsy Results at Month 48

   Time frame: At Month 48

   Subjects with negative and positive cervical biopsy results for only CIN1, only CIN2, only CIN3, CIN1 and CIN2, CIN1 and CIN3, CIN2 and CIN3, CIN1 and CIN2 and CIN3, AIS, Invasive malignancy, other.

   CIN = Cervical intraepithelial neoplasia. CIN1/CIN2/CIN3 = Cervical intraepithelial neoplasia grade 1/grade 2/grade 3.

   Note: Only CIN1/Only CIN2/Only CIN3 categories contain the subject who has only CIN1/CIN2/CIN3, but not the combinations.

8. Number of Subjects With Treatment Referrals by Treatment Type at Month 12

   Time frame: At Month 12

   If a high-grade lesion was detected, the subject was to be referred to treatment according to local medical practice. Any further management following local cervical therapy for cervical lesions was to be handled according to local medical practice within the local health care system. The subject's participation in the study concluded after treatment.

   The treatment types included the following: Loop excision of cervix, Loop cone of cervix, Cold knife cone of cervix, Laser excision, other.

9. Number of Subjects With Treatment Referrals by Treatment Type at Month 24

   Time frame: At Month 24

   If a high-grade lesion was detected, the subject was to be referred to treatment according to local medical practice. Any further management following local cervical therapy for cervical lesions was to be handled according to local medical practice within the local health care system. The subject's participation in the study concluded after treatment.

   The treatment types included the following: Loop excision of cervix, Loop cone of cervix, Cold knife cone of cervix, Laser excision, other.

10. Number of Subjects With Treatment Referrals by Treatment Type at Month 36

    Time frame: At Month 36

    If a high-grade lesion was detected, the subject was to be referred to treatment according to local medical practice. Any further management following local cervical therapy for cervical lesions was to be handled according to local medical practice within the local health care system. The subject's participation in the study concluded after treatment.

    The treatment types included the following: Loop excision of cervix, Loop cone of cervix, Cold knife cone of cervix, Laser excision, other.

11. Number of Subjects With Treatment Referrals by Treatment Type at Month 48

    Time frame: At Month 48

    If a high-grade lesion was detected, the subject was to be referred to treatment according to local medical practice. Any further management following local cervical therapy for cervical lesions was to be handled according to local medical practice within the local health care system. The subject's participation in the study concluded after treatment.

    The treatment types included the following: Loop excision of cervix, Loop cone of cervix, Cold knife cone of cervix, Laser excision, other.

12. Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Withdrawal

    Time frame: From Month 12 [i.e. 12 months after the last visit in HPV-008 (NCT00122681) primary study) up to Month 48 [i.e. 48 months after the last visit in HPV-008 (NCT00122681) primary study]

    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

13. Number of Subjects With Any Fatal SAEs, With Any SAEs Assessed as Possibly Related to Study Participation or to a Concurrent GSK Medication.

    Time frame: From Month 12 [i.e. 12 months after the last visit in HPV-008 (NCT00122681) primary study) up to Month 48 [i.e. 48 months after the last visit in HPV-008 (NCT00122681) primary study]

    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.