Evaluation of a mHealth Intervention to Increase Adherence to Triage of Self-collected HPV+ Women (ATICA Project)

Study Overview
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Brief Summary
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Background Human Papillomavirus (HPV) self-collection offered by community health workers (CHWs) during home visits has been hampered by low levels of triage Pap among HPV-positive women. We investigated effectiveness of a mHealth intervention to increase adherence to triage Pap. Methods We conducted a hybrid type I cluster randomised effectiveness-implementation trial in Jujuy, Argentina. CHWs (clusters) were eligible if actively offering HPV self-collection and served at least 26 women aged 30 years and over. Women were eligible if they conducted self-collection and provided a mobile phone number. 260 CHWs were randomly allocated (3:2 ratio) to a multi-component intervention (Up to four SMS messages sent to HPV-positive women, and one SMS message to CHWs to prompt a visit of women with no triage Pap 60 days after a positive-test), or control group (Usual care: Women instructed to attend their health centre 30 days after HPV self-collection to pick-up results). The primary effectiveness outcome was percentage of HPV-positive women with triage 120 days after the HPV-test result. We evaluated implementation of the intervention using the RE-AIM framework. Funding National Cancer Institute of the National Institutes of Health (USA) under Award Number R01CA218306.

Detailed Description
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Cervical cancer is a disease of health and gender inequalities, and is primarily a cancer of poor, socially vulnerable women. Even though it is almost entirely preventable, in Latin America it is the leading cause of cancer death among women.1 In Argentina, it is the second cause of female cancer death: every year 5,000 women are diagnosed with cervical cancer and more than 1,800 die from the disease. In this country, and generally across Latin America, high mortality is related to problems in the continuity of the prevention process, including low screening coverage and loss to follow-up, diagnosis, and treatment. New screening tests detect the presence of high-risk types of HPV which cause cervical cancer. HPV tests have important advantages over the Pap as a primary screening test, including higher sensitivity (over 90%) and a high negative predictive value, which allow reduced screening frequencies. Very importantly, through self-collection strategies, HPV testing can reduce barriers to screening and increase coverage. HPV self-collection is highly accurate, and is acceptable among women in different countries. However, HPV screening identifies women who are HPV+ (around 10%). Triage tests for HPV+ women determine those who need additional diagnostic procedures. While several triage methods are available for detecting precancerous lesions, including cytology and colposcopy, to date most such triage methods require HPV+ women to attend health centers to determine appropriate follow-up. Although adherence to follow-up and treatment is a widespread problem for cervical cancer programs in Latin America, evidence for interventions to improve adherence to follow-up is lacking. Aims of the study To evaluate the effectiveness of a mHealth intervention targeted to women and health providers to increase adherence to cytological triage among self-tested HPV+ women compared to usual practice. To identify and understand the processes and factors which contribute to the success of the mHealth intervention strategy (or lack thereof). Setting: Jujuy province is located in northwest Argentina and 85% of its population lives in urban areas. The primary health care (PHC) system has 270 health centres and employs about 700 full-time CHWs who visit approximately 110,000 households twice a year for health-related tasks. Since 2012, HPV-testing has been the primary CC screening test, available for women aged 30 years or older attending public health centres. Women are screened with HPV-testing every five years. Since 2014, HPV self-collection is offered during the CHW routine home visits. Women self-collect samples with a cervical sampler kit (Qiagen, Gaithersburg, MD, USA), which is comprised of a cervical brush, specimen container, and transport medium. Community health workers transport specimens at room temperature to health centres; from where they are sent to the provincial HPV laboratory to be analysed for 13 high-risk HPV types using hybrid-capture 2, following the manufacturer's instructions. According to the national guidelines, HPV-positive women with self-collected tests must go through cytology (triage Pap), and those HPV-positive women whose triage Paps are classified as atypical squamous cells of undetermined significance or worse (ASCUS+) are referred to colposcopy, then to biopsy if colposcopy images are classified as abnormal following the International Federation of Cervical Pathology and Colposcopy (IFCPC) classification. Women with histologically confirmed cervical intraepithelial neoplasia (CIN) of grade 2 or worse are referred to treatment. All HPV-testing/diagnoses/treatments of women screened in the public health system are registered on the national screening information system (SITAM, for its initials in Spanish). Results of HPV tests and triage Paps are instantly available online to providers at public health establishments. Participant eligibility and recruitment We regarded CHWs as clusters and judged them eligible if they were actively offering HPV self-collection, that is, they had offered HPV self-collection during the three years preceding the study (2014-2017). We also required that eligible CHWs served a population of at least 26 target women (aged 30 years and older with no HPV testing in the last five years). The rationale for this was the following: Assuming approximately 13% of women with self-collected tests would be positive and conservatively assuming that 60% of these women would be willing to participate in the study, a CHW serving 26 women aged 30 years and over would contribute, in average, with at least two HPV-positive women to the study. A woman was eligible if she performed HPV self-collection during the CHW home visit; and was able to provide a mobile phone number. All women satisfying the eligibility criteria were invited to participate by the CHW and signed a written informed consent. Randomisation and masking Eligible CHWs were classified into four groups according to gender and the area where they worked (urban/rural areas), and a stratified sample of 260 CHWs was randomly selected with allocation proportional to strata. All CHWs were assigned to the trial arms at the same time guaranteeing allocation concealment. Regarding women's consent, the CHWs were instructed to invite the woman and seek consent before disclosing their group allocation. Blinding of intervention and outcome assessments was not feasible due to the characteristics of the study. Intervention development The intervention was rooted in the Health Belief Model (HBM) as described elsewhere, anticipating that the SMS messages would serve as specific cues to action and stimulate triage behaviour. The CHW visit would be an additional cue to action to non-adherent women, as well as an opportunity to provide counselling and support which will change women's perceived benefits of and barriers to screening, as well as the perceived threat of CC. We expected both components of the intervention to increase adherence to triage in the intervention group. In addition, the HBM guided formative research carried out to inform the design of the multicomponent intervention: Firstly, focus group (FGs) included discussions with women to incorporate in the SMS messages a persuasive element that would reinforce the SMS message as a cue to action from women point of view. Secondly, formative research provided information on women´s individual beliefs regarding CC, HPV testing and triage that was used to train CHWs about messages and support to be provided during their visit of positive women who had not been to triage at 60 days. We also developed an automated messaging system (MATYS) that connected asynchronously with SITAM to identify women and CHWs to whom messages should be sent. MATYS was designed to register data on delivery and receipt of SMS messages; a phone number was considered valid if MATYS did not kick back an error notification signalling the number was non-existent. The intervention was planned in consultation with staff from the National Program on Cervical Cancer Prevention (NPCCP), the Jujuy Ministry of Health, the HPV laboratory at Pablo Soria Hospital, and women (through formative research and pilot testing) with the goals of high acceptability and feasibility, and widespread usability. The intervention was also designed to reduce the number of CHW visits aimed at providing women with counselling and support. Procedures CHWs from both groups identified eligible women and invited them to participate during their routine home visits. Once women have performed HPV self-collection, they checked the eligibility criteria and invited them to participate in the study. Once women consented, the CHWs described the procedures according to the group the CHW was allocated to. Women with HPV-positive self-collected tests recruited by CHWs allocated to the intervention group received a multi-component intervention. Those women with an HPV-negative test received one SMS message stating that HPV results were available at the health center. Intervention first component HPV-positive women received one weekly SMS message over a four-week period, notifying that HPV results were available and that they should attend the health centre. The final number of SMS messages delivered to HPV-positive women depended on triage Pap adherence, MATYS stopped sending SMS messages when a triage Pap was registered in SITAM. Intervention second component CHWs received an SMS message to visit HPV-positive women who did not have a triage Pap registered 60 days after the HPV result. Although initially we had planned to send an e-mail to the CHWs, during the training sessions we learned that many CHWs did not use their e-mail account. Therefore, MATYS delivered both an SMS message and an e-mail. The SMS message and e-mail included a secure link to MATYS giving access to information regarding the non-adherent women. Then, they should visit those women to provide counselling about the importance of triage and encourage them to attend the health centre for triage in the following 30 days. The intervention evaluation only includes outcomes related to SMS messages. Once women had performed HPV self-collection, CHWs allocated to intervention explained the sequence and content of SMS messages, and that they might come back for a personal visit. Women with HPV-positive self-collected tests participating in the control group received usual care: once they performed HPV self-collection offered by CHWs during the home visits, women were instructed by CHWs to attend their health centre within 30 days after the HPV self-collection, to pick-up results. RCT outcome measures The primary outcome was the percentage of HPV-positive women with triage 120 days after the HPV result. The secondary outcome was the percentage of HPV-positive women with triage 60 days after the HPV result, which measures the effect of the first component of the intervention - i.e., SMS messages sent to women. Date of HPV result was defined as the date the result was uploaded to SITAM. In addition, we are presenting the following additional data on the care continuum (screening, diagnosis, and treatment), which is essential for effective disease prevention: a. The percentage of HPV-positive women with abnormal triage Paps (ASCUS+) who had colposcopy and biopsy. b. The percentage of women with histologically diagnosed CIN2+ who received treatment. Analysis All analysis conducted on an intention-to-treat (ITT) basis; the effect of the multi-component mHealth intervention on the primary outcome was assessed using a generalized estimating equations approach. The model (logit link and binomial distribution) included the trial group as a fixed effect and CHWs as the clustering variable. Potential effect modifications due to the rural/urban location of the woman and CHW gender was evaluated. Baseline sociodemographic characteristics of the women were compared between groups using the same model with link and distribution selected depending on the variable. Analyses were conducted using STATA 14.0 or SAS v.9.4.

Official Title
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Mixed-Methods Approach to Evaluate a mHealth Intervention to Increase Adherence to Triage of HPV+ Women Who Have Performed Self-collection

Conditions
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Patient Adherence

Intervention / Treatment
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* Other: Multicomponent mHealth Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In the Randomized Controlled Trial we will recruit a minimum of 4000 women, aged 30 and older living in the province of Jujuy, Argentina. Inclusion criteria are: Having performed self-collection of HPV-testing. Mentally competent to understand the consent form. Able to communicate with study staff. Being able to provide a mobile phone telephone number. Exclusion Criteria: Current pregnancy. Women with Mental disability.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Multicomponent mHealth Intervention<br>Women with HPV self-collected tests will receive a multicomponent intervention which includes SMS text messages to remind them to attend triage. In addition, CHWs will receive reminders via e-mails to contact women if after 60 days from the HPV-results HPV+ they have not performed triage. | Other: Multicomponent mHealth Intervention<br>* Women with HPV self-collected tests will receive a multicomponent intervention which includes SMS text messages to remind them to attend triage. In addition, CHWs will receive reminders via e-mails to contact women if after 60 days from the HPV-results HPV+ they have not performed triage<br>|
| No Intervention: Usual Care<br>Women with HPV self-collected tests receive usual care. Upon opting for the HPV self-collected test, women will be instructed to go to the health care center in 30 days to pick up the results. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of women with triage Pap smears at 120 days after HPV results | The percentage of women with triage Pap smears at 120 days after HPV results are registered in the national screening information system (SITAM). This will allow measurement of the overall effect of the multi-component intervention including two periods: a) the 60 day period between the Test results and the SMS message and e-mail sent to Community Health Workers (CHW) (days 1-59); and b) the 60 day period between the SMS message and e-mail sent to CHWs and triage measurement (days 60-120) | 120 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of women with triage Pap smears at 60 days after HPV results | The percentage of women with triage Pap smears at 60 days after HPV results are registered in SITAM (days 1-59). This outcome will allow us to measure the individual effect of the SMS messages sent to women (before CHWs receive prompts to contact non compliant HPV+ women). | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mHealth, cervical cancer prevention, self-collection HPV test, Argentina