Effectiveness of Cervical Screening in Unvaccinated, Herd Effect Protected Women (HPV400)

Cervical Intraepithelial Neoplasia Grade 2/3 Clinical Trial

— HPV400  

Official title:

Effectiveness of Cervical Screening in Unvaccinated, Herd Effect Protected Women - A Randomized Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04755517
• Other study ID #: HPV400
• Status: Enrolling by invitation
• Phase: N/A
• Start date: June 9, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2021
• Source: Tampere University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 14000
• Est. completion date: December 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 25 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma in Situ
• Cervical Intraepithelial Neoplasia
• Cervical Intraepithelial Neoplasia Grade 2/3
• Neoplasms

Intervention

Other:
• Frequent information of cytological/ HPV DNA screening results
All participants will be referred to pertinent diagnosis and treatment according to local standard of care (Käypä hoito 2010) should the cytological screening results (HSIL, ASC-H, AGC-FN) or three consecutive LSIL findings at repeated control visits within 3 years indicate it. The most common screening results (ASCUS, LSIL) are, however, not convened to arm A2 participants before age 28. All cytology and HPV DNA results results are being revealed to all trial participants at age 28 at the study end.

Locations

Country	Name	City	State
Finland	HPV-tutkimukset	Hämeenlinna
Finland	HUS	Helsinki
Finland	HPV-tutkimukset	Iisalmi
Finland	HPV-tutkimukset	Joensuu
Finland	HPV-tutkimukset	Jyväskylä
Finland	Nuorisotutkimusasema, PSHP/ Tampereen yliopisto	Kemi
Finland	Nuorisotutkimusasema, PSHP/Tampereen yliopisto	Kotka
Finland	HPV-tutkimukset	Kouvola
Finland	Nuorisotutkimusasema, PSHP; Tampereen yliopisto	Kuopio
Finland	Nuorisotutkimusasema, PSHP/ Tampereen yliopisto	Lahti
Finland	HPV-tutkimukset	Oulu
Finland	HPV-tutkimukset	Pori
Finland	HPV-tutkimukset	Porvoo
Finland	Nuorisotutkimusasema, PSHP; Tampereen yliopisto	Rauma
Finland	HPV-tutkimukset	Sastamala
Finland	HPV-tutkimukset	Seinäjoki
Finland	Nuorisotutkimusasema; PSHP/ Tamereen yliopisto	Tampere
Finland	HPV-tutkimukset	Varkaus

Sponsors (4)

Lead Sponsor	Collaborator
Tampere University Hospital	European Union, Karolinska Institutet, Tampere University

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The difference between arm A1 vs. arm C	No significant difference in the incidence ratios of CIN2/3 between arms A1 (participants under herd protection and frequently informed of the cytological results) vs. C (participants not under herd protection and frequently informed of the cytological findings) at the age of 28	Three years of follow up within 2020 - 2025
Primary	The difference between arm A2 vs. arm C	No significant difference in the incidence ratios of CIN2/3 between arms A2 (participants under herd protection and frequently informed of the cytological results) vs. C (participants not under herd protection and frequently informed of the cytological findings) at the age of 28.	Three years of follow up within 2020 - 2025
Secondary	Quality of life in infrequently vs. frequently screened unvaccinated women (RAND 36)	The difference between infrequently and frequently screened unvaccinated women at the age of 28 is measured using RAND 36 to measure quality of life. It consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.	Three years of follow up within 2021 - 2025
Secondary	Quality of life in infrequently vs. frequently screened unvaccinated women (EQ-VAS)	The difference between infrequently and frequently screened unvaccinated women at the age of 28 is measured using EQ-VAS a vertical visual analogue scale on which patients provide a global assessment of their health. The scale takes values between 100 (best imaginable health) and 0 (worst imaginable health).	Three years of follow up within 2021 - 2025
Secondary	Quality of life in infrequently vs. frequently screened unvaccinated women (CECA 10)	The difference between infrequently and frequently screened unvaccinated women at the age of 28 is measured using CECA 10, a Spanish acronym for the Specific Questionnaire for Condylomata Acuminata, summary scores of the emotional and sexual activity dimensions will be derived from CECA 10 scales. The CECA questionnaire includes 10 questions across 2 domains: emotional and sexual activity. CECA scores range from 0 (worst HRQL) to 100 (best HRQL)	Three years of follow up within 2021 - 2025