Clinical trial NCT04755517: Effectiveness of Cervical Screening in Unvaccinated, Herd Effect Protected Women (HPV400)
Official title: Effectiveness of Cervical Screening in Unvaccinated, Herd Effect Protected Women - a Randomized Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Cervical Intraepithelial Neoplasia Grade 2/3
Adenocarcinoma in Situ
Keywords: Cervical Intraepithelial Neoplasia
Neoplasms
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma in situ
Lead sponsor: Tampere University Hospital
Sponsor class: OTHER
Collaborators: name: Tampere University
name: European Union
name: Karolinska Institutet
First posted: 2021-02-16
Enrollment: 14000
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: To identify: 1) Whether being informed infrequently results about screening is at least as a) safe and b) accurate as frequently obtaining all information from (the present combination of opportunistic/organized) cervical screening by comparing regimen results of two screening visits at the ages of 25 and 28 years (Arm A1) vs. results of one screening visit at the age of 28 years (Arm A2) in unvaccinated herd effect protected women. Unvaccinated, frequently screened women, who are not under herd effect protection will be controls (C).

Detailed description: Altogether 14.000 1995-1997 born women resident in communities where herd effect against high-risk HPV infections was created with gender-neutral vaccination of birth cohorts 1992-1995 (A-communities) or not (control C-communities) in 2007-2010 with the bi-valent HPV16/18 vaccine will be invited to participate a randomized screening trial at the ages of 25 and 28 years.

Cervical samples will be analysed for HPV DNA with MGP (Modified General Primer) primer system followed by MALDITOF(matrix assisted laser desorption ionization-time of flight mass spectrometry) mass spectrometry on the SEQUENOM (translation of genomic science into solutions for molecular medicine and biomedical research) platform (HPV).

With assumed 65% and 90% participation and retain rates the trial has 80% power to show non-inferiority of the infrequent vs. the frequent screening information.

At the study-end testing the null hypotheses of no difference in the incidence of the CIN2/3 (cervical squamous intraepithelial neoplasia 2/3) end-points comparing the A1 vs. C and A2 vs. C intervention arms will be done using the Mantel-Haenszel one degree of freedom chi-square statistics.

Work Content Letters of invitation to visit cervical screening at the nearest FICAN (Comprehensive Cancer Center Finland)-Mid study site will be send to the approximately 14.000 unvaccinated women at the ages of 25 and 28 years Following informed consent cervical liquid-based cytology samples will be taken for HPV DNA and/or cytology screening at study visits.

All cytological screening results will be communicated to Arm A1 and Arm C study participants. Arm A2 participants will get the test results at the age of 28. However, results of the cytology testing indicative of colposcopy according to local standard of care and currently accepted EU (the European Union) -guidelines (Käypä Hoito 2010, Franceschi et al. 2011) will be immediately communicated to all study participants. HPV DNA results will be communicated to all study participants at the study end. Pertinent colposcopy referrals to organized health care will be made.

All study participants will be offered a possibility to give an oropharyngeal sputum sample after 30 seconds gargling of sterile physiological saline (5 ml) for HPV PCR (polymerase chain reaction) analysis.

Eligibility criteria: Inclusion Criteria:

* Born 1995-1997. 25 years of age residence in one of the eight community-randomized trial A communities with documented herd effect from gender-neutral vaccination or C communities devoid of the herd effect.

Exclusion Criteria:

* Immune compromising disease status (e.g. transplant recipients). HPV vaccination

Primary outcomes:
measure: The difference between arm A1 vs. arm C
timeFrame: Three years of follow up within 2020 - 2025
measure: The difference between arm A2 vs. arm C
timeFrame: Three years of follow up within 2020 - 2025
Secondary outcomes:
measure: Quality of life in infrequently vs. frequently screened unvaccinated women (RAND 36)
timeFrame: Three years of follow up within 2021 - 2025
measure: Quality of life in infrequently vs. frequently screened unvaccinated women (EQ-VAS)
timeFrame: Three years of follow up within 2021 - 2025
measure: Quality of life in infrequently vs. frequently screened unvaccinated women (CECA 10)
timeFrame: Three years of follow up within 2021 - 2025
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: HUS
city: Hämeenlinna
country: Finland
facility: HPV-tutkimukset
city: Iisalmi
country: Finland
facility: HPV-tutkimukset
city: Joensuu
country: Finland
facility: HPV-tutkimukset
city: Jyväskylä
country: Finland
facility: HPV-tutkimukset
city: Kemi
country: Finland
facility: Nuorisotutkimusasema, PSHP/ Tampereen yliopisto
city: Kotka
country: Finland
facility: Nuorisotutkimusasema, PSHP/Tampereen yliopisto
city: Kouvola
country: Finland
facility: HPV-tutkimukset
city: Kuopio
country: Finland
facility: Nuorisotutkimusasema, PSHP; Tampereen yliopisto
city: Lahti
country: Finland
facility: Nuorisotutkimusasema, PSHP/ Tampereen yliopisto
city: Oulu
country: Finland
facility: HPV-tutkimukset
city: Pori
country: Finland
facility: HPV-tutkimukset
city: Porvoo
country: Finland
facility: HPV-tutkimukset
city: Rauma
country: Finland
facility: Nuorisotutkimusasema, PSHP; Tampereen yliopisto
city: Sastamala
country: Finland
facility: HPV-tutkimukset
city: Seinäjoki
country: Finland
facility: HPV-tutkimukset
city: Tampere
country: Finland
facility: Nuorisotutkimusasema; PSHP/ Tamereen yliopisto
city: Varkaus
country: Finland
facility: HPV-tutkimukset
Study officials:
affiliation: Tampere University
name: Matti Lehtinen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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, 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: 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: 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.