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

Study Overview
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Brief Summary
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This study is designed to provide up to four years of annual oncogenic HPV DNA testing and cervical cytology examination for NCT00122681 study subjects who displayed normal cervical cytology but tested positive for oncogenic HPV infection at their last NCT00122681 study visit (Visit 10, Month 48). This follow-up study will also be offered to subjects who were pregnant at their last NCT00122681 study visit (Visit 10, Month 48) so that no cervical sample could be collected at that visit. The objectives & outcome measures of the primary phase (study 008/580299) are presented in a separate protocol posting (NCT00122681).

Official Title
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Gynaecological Follow-up of a Subset of 580299/008 Study Subjects

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Other: Gynaecological follow-up


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from the subject prior to enrolment. Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. A subject previously enrolled in the study NCT00122681 and who fulfils either of the following criteria: displayed normal cervical cytology but tested positive for oncogenic HPV infection at her last NCT00122681 study visit (Visit 10, Month 48). or - was pregnant at her last visit of the NCT00122681 study (Visit 10, Month 48) so that no cervical sample could be collected at that visit. Exclusion Criteria: A subject who displayed normal cervical cytology and who was negative for oncogenic HPV infection at her last NCT00122681 study visit (Visit 10, Month 48). A subject who had a cervical lesion at her last NCT00122681 study visit (Visit 10, Month 48) or who had a cervical lesion that required treatment at the NCT00122681 exit colposcopy. A subject for whom the cervical cytology results from the last NCT00122681 study visit (Visit 10, Month 48) were unavailable for reasons other than pregnancy. If at the time of enrolment the subject experiences heavy bleeding (menstruation or other) or heavy vaginal discharge, or is pregnant, the pelvic exam cannot be performed. The subject's first study visit will be deferred until condition is resolved according to investigator's medical judgment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HPV-052 study subjects Group<br>The study group consisted of a subset of HPV-008 (NCT00122681) study subjects (15-25 years old at first study vaccination), who at their last study visit (Visit 10, Month 48) in HPV-008 (NCT00122681) study displayed normal cervical cytology, but were tested positive for oncogenic HPV infection, or were pregnant and hence no cervical sample could be collected at their HPV-008 (NCT00122681) concluding visit. | Other: Gynaecological follow-up<br>* Subjects received a gynaecological follow-up with cytology and oncogenic HPV DNA testing every 12 months, for up to four years in this gynaecological follow-up study (HPV-052 EXT 008). No vaccine was administered in this extension study. Subjects received 3 doses of Cervarix/Havrix vaccine, administered intramuscularly, according to a 0, 1, 6-month vaccination schedule in the HPV-008 (NCT00122681) primary study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With HPV DNA in Cervical Samples by Hybrid Capture 2 Test (HCII) | 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). | At Months 12, 24, 36, 48 | 
| Number of Subjects With Colposcopy Referral and Colposcopy Adequacy | 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. | At Months 12, 24, 36, 48 | 
| Number of Subjects With Cytological Abnormalities in Cervical Samples by ThinPrep PapTest | 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. | At Months 12, 24, 36, 48 | 
| Number of Subjects With Cervical Biopsy Results 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. | At Month 12 | 
| Number of Subjects With Cervical Biopsy Results 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. | At Month 24 | 
| Number of Subjects With Cervical Biopsy Results 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. | At Month 36 | 
| Number of Subjects With Cervical Biopsy Results 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. | At Month 48 | 
| Number of Subjects With Treatment Referrals by Treatment Type 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. | At Month 12 | 
| Number of Subjects With Treatment Referrals by Treatment Type 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. | At Month 24 | 
| Number of Subjects With Treatment Referrals by Treatment Type 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. | At Month 36 | 
| Number of Subjects With Treatment Referrals by Treatment Type 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. | At Month 48 | 
| Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Withdrawal | 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. | 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] | 
| Number of Subjects With Any Fatal SAEs, With Any SAEs Assessed as Possibly Related to Study Participation or to a Concurrent GSK Medication. | SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. | 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] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, Papillomavirus, Human papillomavirus, Cervical cancer, HPV vaccine