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

Tampere University Hospital

Status: Invitation-only

Conditions: Adenocarcinoma in Situ; Cervical Intraepithelial Neoplasia Grade 2/3

Treatments: Other: Frequent information of cytological/ HPV DNA screening results

Study type: Interventional

Funder types: Other

Identifiers

NCT04755517

HPV400

Details and patient eligibility

About

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).

Full 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.

Enrollment: 14,000 estimated patients

Sex: Female

Ages: 25 to 25 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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14,000 participants in 3 patient groups

A1

Active Comparator group

Description:

Frequent information of screening results for cytology and/or HPV DNA at the ages of 25 (cytology only) and 28 (cytology only) vs A2

Treatment:

Other: Frequent information of cytological/ HPV DNA screening results

A2

No Intervention group

Description:

infrequent information of cytological screening/ HPV DNA results, only at the age 28 years.

C

Active Comparator group

Description:

The third arm with at 8000 participants devoid of herd effect protection and frequent screening at ages 25 and 28 is enrolled for comparative analyses between A1 vs. C and A2 vs. C.

Treatment:

Other: Frequent information of cytological/ HPV DNA screening results