Strategies to Increase Cervical Cancer Screening With Mailed Human Papillomavirus Self-Sampling Kits: A Randomized Clinical Trial

Abstract

Importance: Optimal strategies for increasing cervical cancer screening may differ by patient screening history and health care setting. Mailing human papillomavirus (HPV) self-sampling kits to individuals who are overdue for screening increases adherence; however, offering self-sampling kits to screening-adherent individuals has not been evaluated in the US.

Objective: To evaluate the effectiveness of direct-mail and opt-in approaches for offering HPV self-sampling kits to individuals by cervical cancer screening history (screening-adherent and currently due, overdue, or unknown).

Design, setting, and participants: Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Individuals aged 30 to 64 years with female sex, a primary care clinician, and no hysterectomy were identified through electronic health records (EHRs) and enrolled between November 20, 2020, and January 28, 2022, with follow-up through July 29, 2022.

Interventions: Individuals stratified as due (eg, at the time of randomization, these individuals have been previously screened and are due for their next screening in ≤3 months) were randomized to receive usual care (patient reminders and clinician EHR alerts [n = 3671]), education (usual care plus educational materials about screening [n = 3960]), direct mail (usual care plus educational materials and a mailed self-sampling kit [n = 1482]), or to opt in (usual care plus educational materials and the option to request a kit [n = 3956]). Individuals who were overdue for screening were randomized to receive usual care (n = 5488), education (n = 1408), or direct mail (n = 1415). Individuals with unknown history for screening were randomized to receive usual care (n = 2983), education (n = 3486), or to opt in (n = 3506).

Main outcomes and measures: The primary outcome was screening completion within 6 months. Primary analyses compared direct-mail or opt-in participants with individuals randomized to the education group.

Results: The intention-to-treat analyses included 31 355 randomized individuals (mean [SD] age, 45.9 [10.4] years). Among those who were due for screening, compared with receiving education alone (1885 [47.6%]), screening completion was 14.1% (95% CI, 11.2%-16.9%) higher in the direct-mail group (914 [61.7%]) and 3.5% (95% CI, 1.2%-5.7%) higher in the opt-in group (2020 [51.1%]). Among individuals who were overdue, screening completion was 16.9% (95% CI, 13.8%-20.0%) higher in the direct-mail group (505 [35.7%]) compared with education alone (264 [18.8%]). Among those with unknown history, screening was 2.2% (95% CI, 0.5%-3.9%) higher in the opt-in group (634 [18.1%]) compared with education alone (555 [15.9%]).

Conclusions and relevance: Within a US health care system, direct-mail self-sampling increased cervical cancer screening by more than 14% in individuals who were due or overdue for cervical cancer screening. The opt-in approach minimally increased screening. To increase screening adherence, systems implementing HPV self-sampling should prioritize direct-mail outreach for individuals who are due or overdue for screening. For individuals with unknown screening history, testing alternative outreach approaches and additional efforts to document screening history are warranted.

Trial registration: ClinicalTrials.gov Identifier: NCT04679675.

Figure 1.. Recruitment, Randomization, and Flow in the Self-Testing Options in the Era for Primary HPV Screening for Cervical Cancer (STEP) Trial

^aAfter assessment for eligibility and exclusion, those eligible for randomization were stratified into 3 groups: due for screening, overdue for screening, or unknown screening history. ^bResearch funding constraints necessitated weekly enrollment targets to meet overall accrual targets. If the number eligible in a given week exceeded the target, a sample of individuals was programmatically randomly selected for randomization. ^cIndicates Kaiser Permanente Washington.

Figure 2.. Diagram of Cervical Cancer Screening Outcomes

^aKit requested by 485 individuals. ^b39 Other high-risk HPV-positive only and 5 unsatisfactory results. ^c32 Other high-risk HPV-positive only and 7 unsatisfactory results. ^d2 Returned kits untested (1 received beyond specimen stability and 1 with mold on the swab) and rescreened in clinic <6 mo postrandomization; and 6 returned a tested kit after in-clinic screening (kit results did not impact outcomes). ^e20 Requested a kit but completed in-clinic screening (1 returned a kit untested [mold on the swab] and rescreened in clinic <6 mo postrandomization; and 4 returned a kit after in-clinic screening [kit results did not impact outcomes]). ^f17 Other high-risk HPV-positive only and 3 unsatisfactory results. ^g3 Returned a kit after in-clinic screening (kit results did not impact outcomes). ^hKit requested by 157 individuals. ⁱ10 Other high-risk HPV-positive only and 2 unsatisfactory results. ^j7 Requested a kit but completed in-clinic screening. ^k1 Returned a kit untested (mold on the swab) and did not rescreen in clinic <6 mo postrandomization.

Figure 3.. Cumulative Incidence of Screening Completion by Randomization Group, by Screening History