Effectiveness of Cervical Screening in HPV Vaccinated Women

Study Overview
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Brief Summary
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The main objective of the study is to identify whether or not being informed infrequently results about screening is: 1) At least as safe and accurate as frequently obtaining all information from the present combination of opportunistic/organized cervical screening by comparing regimen results of three screening visits at the ages of 22, 25 and 30 years (Arm A1) vs. results of one screening visit at the age of 30 years (Arm A2) in Human papillomavirus (HPV) vaccinated young women.

Detailed Description
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Altogether 16.500 1992-1995 born women vaccinated with the bi-valent human papillomavirus type 16 and 18 (HPV16/18) vaccine as adolescents either at the age of 12 to 15 or at the age of 18 will be invited to an effectiveness trial at the age of 22 years, and randomized into Arms A1 and A2, and A3, respectively. Cervical samples and cervico-vaginal self-samples rinsed in first-void urine will be analysed for HPV and C. trachomatis DNA with MGP primer system followed by MALDITOF mass spectrometry on the SEQUENOM platform (HPV) and the Abbott™ PCR (Chlamydia trachomatis), respectively. With assumed >50% participation the trial has 80% power to show non-inferiority of the infrequent vs. the frequent screening information. A one-way (participant) blinded interim analysis among the 1992-born study participants in A1 and A3 arms, who have attended the 2nd study visit at the age of 25 years, will be performed in 2017 for assuring no statistically significant differences in the cervical intraepithelial neoplasia grade 2/3 (CIN2/CIN3) incidences of the two arms. At the study end testing the null hypotheses of no difference in the incidence of the CIN2/3 end-points between the A1 and A2 intervention arms will be done using the Mantel-Haenszel one degree of freedom chi-square statistics.

Official Title
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Effectiveness of Cervical Screening in HPV Vaccinated Women - A Randomized Trial

Conditions
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Cervical Intraepithelial Neoplasia Grade 2/3

Intervention / Treatment
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* Other: Cytological screening in A1 and A3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HPV 16/18 vaccinated. Born 1992-1995. Exclusion Criteria: Immunocompromising disease. HPV 6/11/16/18 vaccination.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 22 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A1<br>A1) Cytological screening in A1 and A3. Frequent information of screening results for cytology and/or HPV DNA at the ages of 22 (cytology only), 25 and 30. | Other: Cytological screening in A1 and A3<br>* Cytological screening.<br>|
| No Intervention: A2<br>A2) infrequent information of screening results, only at the age 30 years. | |
| Other: A3<br>A3) Cytological screening in A1 and A3. With at least 1000 participants is enrolled for interim safety analysis when the 1992 birth cohort is 25 years of age and cytology results are being revealed. | Other: Cytological screening in A1 and A3<br>* Cytological screening.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of intraepithelial neoplasia grade 2/3 (CIN2/3). | 1a) No marked difference in the incidence of CIN2/3 between arms A1 (participants frequently informed of the cytological results) and A3 (participants not informed of the cytological findings at the age of 22) (interim analysis). 1b) No difference in the incidence of CIN2/3 between arms A1 (participants frequently informed of the cytological results) and A2 (participants infrequently informed of the cytological results). The participants will be followed for 9 years starting from the year they turn 22. For 1992 born the follow-up will start in 2014 and end in 2023. For 1995 born the follow-up will start in 2017 and end in 2026. The interim analysis will include only 1992 cohort. The final analysis will include all cohorts (1992, 1993, 1994, 1995). | 2017(interim), 2026 (final analysis). Participants will be followed for the duration of the study until 2026, an expected average of 9 years. |