Reengineering Cervical Cancer Screening for the 21st Century: Joint Action for a Novel Up-to-date and Sustainable Screening Program

NCT06915610 | Enrolling By Invitation

• 1 other identifier: MPr-2023-12-15422
• Study Type: interventional
• Target: 5,700
• Locations: 1 country
• Sites: 1

Brief Summary

Cervical cancer screening (CCS) is important to prevent and control cervical cancer (CC). In Portugal, CCS starts with the assessment of the presence of Human Papillomavirus (HPV) in cervical-vaginal samples, collected by a health professional. However, self-sampling (self-collection of vaginal samples by the participants in CCS), is being considered in several settings, aiming to improve participation in CCS, while also exploring its potential to reduce costs. The goal of this study is to learn how self-sampling could be introduced in the CCS program in Portugal, by testing different strategies to combine the self-collection of samples with the collection of samples by a health professional, which is currently the standard of care. Researchers will conduct a study comparing the following ways of conducting CCS:

• Sample collection by health professionals - SOC;
• Self-sampling - SS;
• Asking the participants if they prefer to collect their own samples, or to have the samples collected by a health professional, and then proceed as they prefer - CHOICE. After assessing the adherence to CCS in each of the groups define above, the participants will be given the possibility to participate through a method different from the initially proposed or chosen, as follows:
• SOC will be complemented with invitation for SS;
• SS will be complemented with invitation for the SOC;
• CHOICE participants will be invited again to CHOICE, being given a new opportunity to choose how they prefer to be screened. This study design allows for comparisons between these groups, to understand how using these strategies alone and complementarily works, and also for comparisons within each group, to understand how one strategy being used on the top of the previous may contribute to increase adherence to screening. The researchers will additionally collect information of the adherence to CCS in the year before the study is conducted, to be used as an additional benchmark. For a better understanding on the potential barriers and facilitators to incorporating self-sampling in the CCS program, this study will also comprise interviews with the health professionals involved in the study, as well as with females eligible for screening who had been invited to participate. Depending on the results of HPV testing and complementary cytological evaluations, participants may be referred for further assessment, according to the standard of care in the Portuguese National Health Service. This study will address the possibility of improving the yielding of the referral for further assessment, by testing, in parallel to the current standard of care, a method that is expected to contribute to reducing the number of referrals of false-positives. Therefore, this study is expected to provide evidence based on different methods of assessment, showing the extent to which SS may contribute to improve adherence do CCS, and testing new methods that may reduce the referral of false-positives for further assessment.

Conditions

Cervical Cancer Screening

Keywords

Cervical cancer; Human papillomavirus; Self-sampling; DNA methylation

Outcome Measures

Primary Outcomes (3)

• Adherence to screening, after the first invitation for CCS in the study

  Proportion of invited females, in each arm, who adhere after the first scheduling/invitation (SOC, SS or CHOICE)

  45 days after first scheduling/invitation

• Adherence to CCS, after two invitations for screening in the study

  Proportion of invited females, in each arm, who adhere after the second scheduling/invitation (SOC+SS, SS+SOC or CHOICEx2)

  45 days after first scheduling/invitation or 45 days after the second scheduling/invitation (for those not adhering to the first scheduling/invitation within 45 days)

• Performance of DNA methylation markers for high-grade squamous intraepithelial lesions or worse (HSIL+) detection

  Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of methylation analysis for detection of high-grade squamous intraepithelial lesions or worse (HSIL+), using the cytological triage results and the histological results as gold-standard

  45 days after cytological or histological results, as applicable

Secondary Outcomes (8)

• Identification of barriers and facilitators to the implementation and participation in CCS

  90 days after the last invitation for CCS in the study

• Proportion of HPV infection, overall and for each genotype tested

  45 days after first scheduling/invitation or 45 days after the second scheduling/invitation (for those not adhering to the first scheduling/invitation within 45 days)

• Adherence to follow-up appointments (%), overall and among participants referred for follow-up

  45 days after the appointment date

• Variation in adherence and HPV test result outcomes between the first and the second invitation for screening

  45 days after first scheduling/invitation or 45 days after the second scheduling/invitation (for those not adhering to the first scheduling/invitation within 45 days)

• Variation in adherence from the previous year to the study period

  45 days after first scheduling/invitation or 45 days after the second scheduling/invitation (for those not adhering to the first scheduling/invitation within 45 days)

Other Outcomes (1)

• Process indicators

  Up to 45 days after first scheduling/invitation or up to 45 days after the second scheduling/invitation (for those not adhering to the first scheduling/invitation within 45 days)

Study Arms (3)

Standard of care (followed by self-sampling for the non-adherent) - SOC+SS

OTHER

CCS screening according to the standard of care (sample collected by a health professional). Participants not adhering will be subsequently invited to perform self-sampling for screening. When considering only the initial use of the SOC for CCS, this corresponds to arm type "active comparator". When considering the use of the SOC, followed by SS for participants not adhering to CCS according to the SOC, this corresponds to arm type "experimental".

Other: Invitation of all participants to CCS according to the standard of care (active comparator); Other: Invitation of all participants to CCS according to the standard of care, followed by invitation of those non-adherent to CCS through self-sampling

Self-sampling (followed by the standard of care for the non-adherent) - SS+SOC

EXPERIMENTAL

CCS screening by self-sampling. Participants not adhering will be subsequently invited for screening according to the standard of care (sample collected by a health professional).

Other: Invitation of all participants to CCS through self-sampling; Other: Invitation of all participants to CCS through self-sampling, followed by invitation of those non-adherent to CCS according to the standard of care

Choice (2x) between CCS through sample collected by health professional and self sampling - CHOICEx2

EXPERIMENTAL

Participants will be asked for their preference for CCS through sample collected by a health professional or by self-sampling, and will undergo CCS accordingly. Those not adhering will be invited again to choose between one of the two methods of CCS.

Other: Invitation of all participants to CCS, asking them to choose between self-sampling and the standard of care; Other: Invitation of all participants to CCS, asking them to choose between self-sampling and the standard of care; this mode of invitation is repeated when participants do not adhere to the first invitation

Interventions

Invitation of all participants to CCS according to the standard of care (active comparator) OTHER

Invitation of all participants to CCS according to the standard of care

Also known as: SOC

Standard of care (followed by self-sampling for the non-adherent) - SOC+SS

Invitation of all participants to CCS through self-sampling OTHER

A self-sampling kit mailed to the participants, with a prepaid envelope for returning them after sample collection. Participants may also return the kits by depositing them in a container that will be available in their Health Care Center. The invitation for CCS through self-sampling is accompanied by written instructions, SMS reminders and navigation support (dedicated telephone line, WhatsApp, website)

Also known as: SS, Evalyn Brush

Self-sampling (followed by the standard of care for the non-adherent) - SS+SOC

Invitation of all participants to CCS, asking them to choose between self-sampling and the standard of care OTHER

In a telephone contact, prompted by an SMS, participants will be given the opportunity to schedule CCS according to the standard of care or to ask for a self-sampling kit to be mailed to them. Depending on their choice, the procedure will be similar to what is described for arm SOC or for arm SS, as applicable

Also known as: CHOICE

Choice (2x) between CCS through sample collected by health professional and self sampling - CHOICEx2

Invitation of all participants to CCS according to the standard of care, followed by invitation of those non-adherent to CCS through self-sampling OTHER

Participants not adhering to CCS after the first invitation (SOC) will be additionally invited for CCS screening through self-sampling (as in SS)

Also known as: SOC+SS

Standard of care (followed by self-sampling for the non-adherent) - SOC+SS

Invitation of all participants to CCS through self-sampling, followed by invitation of those non-adherent to CCS according to the standard of care OTHER

Participants not adhering to CCS after the first invitation for self-sampling (SS) will be additionally invited for CCS screening according to the standard of care (as in SOC)

Also known as: SS+SOC

Self-sampling (followed by the standard of care for the non-adherent) - SS+SOC

Invitation of all participants to CCS, asking them to choose between self-sampling and the standard of care; this mode of invitation is repeated when participants do not adhere to the first invitation OTHER

Participants not adhering to CCS after a first invitation for screening through a method of their choice (CHOICE) will be invited again, also being given the opportunity to choose between the standard of care or self-sampling (as in the first CHOICE invitation). Depending on the participants' choice, the procedure will be similar to what is described for arm SOC or for arm SS, as applicable, both in the first and in the second CHOICE invitations

Also known as: CHOICEx2

Choice (2x) between CCS through sample collected by health professional and self sampling - CHOICEx2

Eligibility Criteria

• Age: 30 Years - 69 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females fulfilling the eligibility criteria for CCS, as defined by the current guidelines for the organized screening program in Portugal.

You may not qualify if:

• Not having a Portuguese mobile phone number or a Portuguese address available in the clinical/administrative records of the primary healthcare units;

Sponsors & Collaborators

• Instituto de Saude Publica da Universidade do Porto: lead
• Instituto Portugues de Oncologia, Francisco Gentil, Porto: collaborator
• Universidade do Porto: collaborator
• Unidade Local de Saude de Gaia e Espinho EPE: collaborator

Study Sites (1)

Unidade Local de Saúde Gaia e Espinho

Vila Nova de Gaia, 4434-502, Portugal

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Nuno Lunet, PhD

  Universidade do Porto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Within each group, participants will be initially invited for CCS though one of the methods under evaluation, and those not adhering will be invited again for CCS through another method. This design will allow for between-group comparisons, both after the first invitation and considering the two invitations, as well as within-group comparisons to assess the extent to which the second (complementary) invitation may contribute to improve participation in CCS. Additionally, data on the participation in CCS in the same settings in the previous years will be retrospectively collected, allowing further ("before-after") comparisons within each group. A qualitative study will be conducted involving medical doctors and females invited for CCS within the study to assess barriers and facilitators to CCS implementation and participation. An observational design nested within the RCT will be used to assess the experience of females invited for CCS, and determinants of adherence.

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 8, 2025
• Study Start: April 10, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 23, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)