Clinical trial NCT06371118: HPV Self-sampling for Women Who do Not Attend Cervical Cancer Screening Programme
Official title: HPV Self-sampling for Women Who do Not Attend the Organized Cervical Cancer Screening Programme (HERSELF)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Papillomavirus Infections
Early Detection of Cancer
Cervix Cancer
Self-Examination
Lead sponsor: Universidade do Porto
Sponsor class: OTHER
Collaborators: name: Unidade de Saúde Familiar de Garcia de Orta, Porto
name: Unidade de Saúde Familiar da Prelada, Porto
name: Unidade de Saúde Familiar de Cedofeita, Porto
name: Instituto Portugues de Oncologia, Francisco Gentil, Porto
First posted: 2024-04-17
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 26
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This study aims to test the effectiveness and cost-effectiveness of two different strategies of home-delivered HPV self-sampling, in comparison to the standard of care strategy, to increase adherence to cervical cancer screening.

An experimental and population-based study will be implemented at three primary healthcare centers located in the Western Porto region: Cedofeita, Garcia de Orta, and Prelada. Eligible women will be randomized into a control group or an intervention group. The control group will correspond to the standard of care (invitation to screening in a clinical setting). The intervention group will be randomized into two subgroups: 1) a "directly mailed" group that will receive a self-sampling kit at their home addresses by post; 2) an "opt-in" group that will receive an invitation at home asking if they want to receive a self-sampling kit, with a pre-paid envelope to return the answer to this question. Women who answer "yes" will receive the self-sampling kit at their home addresses by post.

Self-sampling samples will be subjected to HPV genotyping. In parallel, high-risk HPV positive women will be called in by their family doctors to undergo screening in a clinical setting so that they can continue their clinical follow-up in the conventional pathway.

Detailed description: The goal of this randomized clinical trial is to test the effectiveness and cost-effectiveness of two different strategies of home-delivered HPV self-sampling to increase the adherence to cervical cancer screening in women who are overdue for cervical cancer screening, in comparison to the standard of care strategy.

The main questions this study aims to answer are:

* To test the effectiveness of an invitation strategy to improve the adherence to cervical cancer screening based on directly home-delivered HPV self-sampling tests + automated reminders, in comparison to the standard of care invitation.
* To test the effectiveness of an invitation strategy to improve the adherence to cervical cancer screening based on home-delivered HPV self-sampling tests using opt-in procedures for ordering the kit + automated reminders, in comparison to the standard of care invitation.
* To compare the cost-effectiveness between a) standard of care; b) directly home-delivered HPV self-sampling tests + automated reminders; and c) home-delivered HPV self-sampling tests using opt-in procedures for ordering the kit + automated reminders.

Eligible women will be randomized (1:1) into a control group and an intervention group:

* Control group: corresponds to the standard of care, which is an invitation to cervical cancer screening in a clinical setting, through a written letter, printed and sent by the primary healthcare unit where the women are registered.
* Intervention group: Women allocated to this group will be randomized (1:1) into two subgroups, described briefly as follows:

  * Intervention 1 (half of the intervention group): HPV self-sampling test mailed directly to the women's home address (directly mailed group), complemented with a SMS reminder. If a woman returns the sample, HPV-type genotyping will be performed. If High-Risk HPV (HR-HPV) is detected, women will be informed of the result and invited to take cervical cancer screening in a clinical setting by their family doctors. Subsequent follow-up will take place according to Portuguese guidelines.
  * Intervention 2 (half of the intervention group): An invitation is mailed to the women´s home address, offering a self-sampling kit, to be ordered by returning a prepaid envelope with the answer "yes" (opt-in group). In the event of a positive response, an HPV self-sampling test is mailed to the women's home, complemented with a SMS reminder. If a woman returns the sample, HPV genotyping will be performed. If HR-HPV is detected, women will be informed of the result and invited to take cervical cancer screening in a clinical setting, performed by their family doctors. Subsequent follow-up will take place according to Portuguese guidelines.

In Interventions 1 and 2, when HR-HPV is detected in the self-sampling test, this sample will be subjected to HPV-DNA methylation testing. If increased HPV DNA methylation is detected and the woman has yet not attended the conventional screening invitation by her family doctor, she will be informed by her family doctor that a new test has indicated an increased risk for cervical cancer and the need to attend a medical appointment will be reinforced.

Eligibility criteria: Inclusion Criteria:

* Women aged between 26 and 60 years old;
* Women eligible for cervical cancer screening whose screening is at least 1 year overdue.

Exclusion Criteria:

* No mobile phone number available at the National Health Service database;
* Foreign mobile phone number;
* No address available at the National Health Service database;
* Foreign address.

Primary outcomes:
measure: Adherence to conventional screening in control group
timeFrame: 45 and 90 days after the conventional screening appointment date
measure: Adherence to HPV self-sampling in intervention 1 (directly mailed) group
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Adherence to HPV self-sampling in intervention 2 (opt-in) group
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Adherence proportion to HPV self-sampling in intervention 1 (directly mailed) group VS Adherence proportion to conventional screening in control group
timeFrame: 45 and 90 days after the day the self-sampling kit is sent or 45 and 90 days after the conventional screening appointment date, as appropriate
measure: Adherence proportion to HPV self-sampling in intervention 2 (opt-in) group VS Adherence proportion to conventional screening in control group
timeFrame: 45 and 90 days after the day the self-sampling kit is sent or 45 and 90 days after the conventional screening appointment date, as appropriate
Secondary outcomes:
measure: Adherence to first follow-up step in control group
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence to first follow-up step in intervention 1 (directly mailed) group
timeFrame: 45 and 90 days after the clinician-sampling appointment date
measure: Adherence to first follow-up step in intervention 2 (opt-in) group
timeFrame: 45 and 90 days after the clinician-sampling appointment date
measure: Adherence to first follow-up step in control group among women referred for follow-up
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence to first follow-up step in intervention 1 (directly mailed) group among women referred for folow-up
timeFrame: 45 and 90 days after the clinician-sampling appointment date
measure: Adherence to first follow-up step in intervention 2 (opt-in) group among women referred for folow-up
timeFrame: 45 and 90 days after the clinician-sampling appointment date
measure: Adherence to colposcopy in control group
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence to colposcopy in intervention 1 (directly mailed) group
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence to colposcopy in intervention 2 (opt-in) group
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence to colposcopy in control group among women referred for colposcopy
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence to colposcopy in intervention 1 (directly mailed) group among women referred for colposcopy
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence to colposcopy in intervention 2 (opn-in) group among women referred for colposcopy
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Timelapse (in days) between the shipment of self-sampling kit and the return of the sample, in intervention 1 (directly mailed) group
timeFrame: Follow-up will end at 90 days
measure: Timelapse (in days) between the invitation to receive a self-sampling kit and the return of the opt-in answer, in intervention 2 (opt-in) group
timeFrame: Follow-up will end at 90 days
measure: Timelapse (in days) between the shipment of self-sampling kit and the return of the sample, in intervention 2 (opt-in) group
timeFrame: Follow-up will end at 90 days
measure: Adherence proportion to first follow-up step in intervention 1 (directly mailed) group VS Adherence proportion to first follow-up step in control group
timeFrame: 45 and 90 days after the first follow-up step (clinician-sampling appointment date or colposcopy appointment date, as appropriate)
measure: Adherence proportion to first follow-up step in intervention 2 (opt-in) group VS Adherence proportion to first follow-up step in control group
timeFrame: 45 and 90 days after the first follow-up step (clinician-sampling appointment date or colposcopy appointment date, as appropriate)
measure: Adherence proportion to first follow-up step in intervention 1 (directly mailed) group among women referred for follow-up VS Adherence proportion to first follow-up step in control group among women referred for follow-up
timeFrame: 45 and 90 days after the first follow-up step (clinician-sampling appointment date or colposcopy appointment date, as appropriate)
measure: Adherence proportion to first follow-up step in intervention 2 (opt-in) group among women referred for follow-up VS Adherence proportion to first follow-up step in control group among women referred for follow-up
timeFrame: 45 and 90 days after the first follow-up step (clinician-sampling appointment date or colposcopy appointment date, as appropriate)
measure: Adherence proportion to colposcopy in intervention 1 (directly mailed) group VS Adherence proportion to colposcopy in control group
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence proportion to colposcopy in intervention 2 (opt-in) group VS Adherence proportion to colposcopy in control group
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence proportion to colposcopy in intervention 1 (directly mailed) group among women referred for colposcopy VS Adherence proportion to colposcopy in control group among women referred for colposcopy
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Adherence proportion to colposcopy in intervention 2 (opt-in) group among women referred for colposcopy VS Adherence proportion to colposcopy in control group among women referred for colposcopy
timeFrame: 45 and 90 days after the colposcopy appointment date
measure: Proportion of HR-HPV positivity in control group
timeFrame: 45 and 90 days after the conventional screening appointment date
measure: Proportion of HR-HPV positivity in intervention 1 (directly mailed) group
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Proportion of HR-HPV positivity in intervention 2 (opt-in) group
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Proportion of HR-HPV positivity in control group among women who adhered to conventional screening
timeFrame: 45 and 90 days after the conventional screening appointment date
measure: Proportion of HR-HPV positivity in intervention 1 (directly mailed) group among women who returned the self-sample
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Proportion of HR-HPV positivity in intervention 2 (opt-in) group among women who returned the self-sample
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Proportion of HR-HPV 16/18 positivity in control group
timeFrame: 45 and 90 days after the conventional screening appointment date
measure: Proportion of HR-HPV 16/18 positivity in intervention 1 (directly mailed) group
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Proportion of HR-HPV 16/18 positivity in intervention 2 (opt-in) group
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Proportion of HR-HPV 16/18 positivity in control group among women who adhered to conventional screening
timeFrame: 45 and 90 days after the conventional screening appointment date
measure: Proportion of HR-HPV 16/18 positivity in intervention 1 (directly mailed) group among women who returned the self-sample
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Proportion of HR-HPV 16/18 positivity in intervention 2 (opt-in) group among women who returned the self-sample
timeFrame: 45 and 90 days after the day the self-sampling kit is sent
measure: Positive predictive value of self-sampling for the detection of HR-HPV, using clinician-sampling results as gold standard
timeFrame: 90 days after clinicial-sampling appointment date
measure: Sensitivity of HR-HPV testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Specificity of HR-HPV testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Positive likelihood ratio of HR-HPV testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Negative likelihood ratio of HR-HPV testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Accuracy of HR-HPV testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Sensitivity of HR-HPV non 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Specificity of HR-HPV non 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Positive likelihood ratio of HR-HPV non 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Negative likelihood ratio of HR-HPV non 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Accuracy of HR-HPV non 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Sensitivity of HR-HPV 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Specificity of HR-HPV 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Positive likelihood ratio of HR-HPV 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Negative likelihood ratio of HR-HPV 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
measure: Accuracy of HR-HPV 16/18 testing and methylation analysis in self-samples, using biopsy results as gold standard
timeFrame: 90 days after the colposcopy appointment date
Other outcomes:
Locations:
city: Porto
country: Portugal
facility: Unidade de Saúde Familiar Cedofeita
city: Porto
country: Portugal
facility: Unidade de Saúde Familiar Prelada
Study officials:
affiliation: Instituto de Saude Publica da Universidade do Porto
name: Maria Margarida MN Teixeira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Saude Publica da Universidade do Porto
name: Nuno Lunet, PhD
role: STUDY_CHAIR
References: