Clinical trial NCT02149030: Effectiveness of Cervical Screening in HPV Vaccinated Women
Official title: Effectiveness of Cervical Screening in HPV Vaccinated Women - a Randomized Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Cervical Intraepithelial Neoplasia Grade 2/3
Lead sponsor: Tampere University
Sponsor class: OTHER
Collaborators: name: European Union
name: Academy of Finland
name: Cancer Society of Finland
First posted: 2014-05-29
Enrollment: 6958
Sex: FEMALE
Minimum age (years): 22
Maximum age (years): 22
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* HPV 16/18 vaccinated. Born 1992-1995.

Exclusion Criteria:

* Immunocompromising disease. HPV 6/11/16/18 vaccination.

Primary outcomes:
measure: Occurrence of intraepithelial neoplasia grade 2/3 (CIN2/3).
timeFrame: 2017-2020, i.e. four years (interim), 2021-2025, i.e. five years (final analysis). Participants will be followed for the duration of the study until 2026, an expected average of 9 years.
Secondary outcomes:
measure: Type-replacement
timeFrame: 2021-2025, i.e. four years
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: HUS
city: Hyvinkää
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Hämeenlinna
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Iisalmi
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Joensuu
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Jyväskylä
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Jämsä
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Kajaani
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Kemi
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Kokkola
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Kotka
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Kouvola
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Kuopio
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Lahti
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Lappeenranta
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Lohja
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Mikkeli
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Oulu
country: Finland
facility: THL
city: Pori
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Porvoo
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Rauma
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Rovaniemi
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Salo
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Savonlinna
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Seinäjoki
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Tampere
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Turku
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Vaasa
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Vammala
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Varkaus
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
city: Äänekoski
country: Finland
facility: Nuorisotutkimusasema: Tampereen yliopisto
Study officials:
affiliation: Tampere University
name: Matti Lehtinen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vanska S, Luostarinen T, Baussano I, Apter D, Eriksson T, Natunen K, Nieminen P, Paavonen J, Pimenoff VN, Pukkala E, Soderlund-Strand A, Dubin G, Garnett G, Dillner J, Lehtinen M. Vaccination With Moderate Coverage Eradicates Oncogenic Human Papillomaviruses If a Gender-Neutral Strategy Is Applied. J Infect Dis. 2020 Aug 17;222(6):948-956. doi: 10.1093/infdis/jiaa099.
citation: Louvanto K, Eriksson T, Gray P, Apter D, Baussano I, Bly A, Harjula K, Heikkila K, Hokkanen M, Huhtinen L, Ikonen M, Karttunen H, Nummela M, Soderlund-Strand A, Veivo U, Dillner J, Elfstom M, Nieminen P, Lehtinen M. Baseline findings and safety of infrequent vs. frequent screening of human papillomavirus vaccinated women. Int J Cancer. 2020 Jul 15;147(2):440-447. doi: 10.1002/ijc.32802. Epub 2019 Dec 16.
citation: Gray P, Kann H, Pimenoff VN, Eriksson T, Luostarinen T, Vanska S, Surcel HM, Faust H, Dillner J, Lehtinen M. Human papillomavirus seroprevalence in pregnant women following gender-neutral and girls-only vaccination programs in Finland: A cross-sectional cohort analysis following a cluster randomized trial. PLoS Med. 2021 Jun 7;18(6):e1003588. doi: 10.1371/journal.pmed.1003588. eCollection 2021 Jun.
citation: Kalliala I, Eriksson T, Aro K, Hokkanen M, Lehtinen M, Gissler M, Nieminen P. Preterm birth rate after bivalent HPV vaccination: Registry-based follow-up of a randomized clinical trial. Prev Med. 2021 May;146:106473. doi: 10.1016/j.ypmed.2021.106473. Epub 2021 Feb 24.
citation: Lehtinen M, Gray P, Louvanto K, Vanska S. In 30 years, gender-neutral vaccination eradicates oncogenic human papillomavirus (HPV) types while screening eliminates HPV-associated cancers. Expert Rev Vaccines. 2022 Jun;21(6):735-738. doi: 10.1080/14760584.2022.2064279. Epub 2022 Apr 15. No abstract available.
citation: Lehtinen M, Pimenoff VN, Nedjai B, Louvanto K, Verhoef L, Heideman DAM, El-Zein M, Widschwendter M, Dillner J. Assessing the risk of cervical neoplasia in the post-HPV vaccination era. Int J Cancer. 2023 Mar 15;152(6):1060-1068. doi: 10.1002/ijc.34286. Epub 2022 Oct 10.
citation: Pimenoff VN, Gray P, Louvanto K, Eriksson T, Lagheden C, Soderlund-Strand A, Dillner J, Lehtinen M. Ecological diversity profiles of non-vaccine-targeted HPVs after gender-based community vaccination efforts. Cell Host Microbe. 2023 Nov 8;31(11):1921-1929.e3. doi: 10.1016/j.chom.2023.10.001.
citation: Lehtinen M, Bruni L, Elfstrom M, Gray P, Logel M, Mariz FC, Baussano I, Vanska S, Franco EL, Dillner J. Scientific approaches toward improving cervical cancer elimination strategies. Int J Cancer. 2024 May 1;154(9):1537-1548. doi: 10.1002/ijc.34839. Epub 2024 Jan 9.
citation: Lehtinen M, Elfstrom M, Vanska S, Dillner J. Elimination of cervical cancer by refined vaccination and screening. Int J Cancer. 2025 Feb 15;156(4):886-888. doi: 10.1002/ijc.35228. Epub 2024 Oct 25. No abstract available.
citation: Louvanto K, Verhoef L, Pimenoff V, Eriksson T, Leppala S, Lagheden C, Gray P, Scibior-Bentkowska D, Sumiec E, Nieminen P, Dillner J, Berkhof J, Meijer CJLM, Lehtinen M, Nedjai B, Heideman DAM. Low methylation marker levels among human papillomavirus-vaccinated women with cervical high-grade squamous intraepithelial lesions. Int J Cancer. 2024 Nov 1;155(9):1549-1557. doi: 10.1002/ijc.35044. Epub 2024 May 27.
citation: Taavela K, Eriksson T, Huhtala H, Bly A, Harjula K, Heikkila K, Hokkanen M, Nummela M, Kotaniemi-Talonen L, Lehtinen M, Louvanto K. The quality of life of frequently vs. infrequently screened HPV vaccinated women. Qual Life Res. 2024 Apr;33(4):941-949. doi: 10.1007/s11136-023-03575-y. Epub 2024 Jan 18.
citation: Lehtinen M, Apter D, Baussano I, Eriksson T, Natunen K, Paavonen J, Vanska S, Bi D, David MP, Datta S, Struyf F, Jenkins D, Pukkala E, Garnett G, Dubin G. Characteristics of a cluster-randomized phase IV human papillomavirus vaccination effectiveness trial. Vaccine. 2015 Mar 3;33(10):1284-90. doi: 10.1016/j.vaccine.2014.12.019. Epub 2015 Jan 12.