Effect of Mailed Human Papillomavirus Test Kits vs Usual Care Reminders on Cervical Cancer Screening Uptake, Precancer Detection, and Treatment: A Randomized Clinical Trial

Abstract

Importance: In the United States, more than 50% of cervical cancers are diagnosed in underscreened women. Cervical cancer screening guidelines now include primary human papillomavirus (HPV) testing as a recommended strategy. Home-based HPV self-sampling is a viable option for increasing screening compliance and effectiveness; however, US data are needed to inform health care system implementation.

Objective: To evaluate effectiveness of mailed HPV self-sampling kits vs usual care reminders for in-clinic screening to increase detection and treatment of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and uptake of cervical cancer screening.

Design, setting, and participants: Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Women aged 30 to 64 years with health plan enrollment for 3 years and 5 months or more, a primary care clinician, no Papanicolaou test within 3 years and 5 months, and no hysterectomy were identified through electronic medical records and enrolled from February 25, 2014, to August 29, 2016, with follow-up through February 26, 2018.

Interventions: The control group received usual care (annual patient reminders and ad hoc outreach from primary care clinics). The intervention group received usual care plus a mailed HPV self-sampling kit.

Main outcomes and measures: Two primary outcomes were (1) CIN2+ detection within 6 months of screening and (2) treatment within 6 months of CIN2+ detection. Screening uptake within 6 months of randomization was a secondary outcome.

Results: A total of 19 851 women (mean [SD] age, 50.1 [9.5] years) were included, with 9960 randomized to the intervention group and 9891 randomized to the control group. All women randomized were included in analysis. In the intervention group, 12 participants with CIN2+ were detected compared with 8 in the control group (relative risk, 1.49; 95% CI, 0.61-3.64) and 12 cases were treated vs 7 in the control group (relative risk, 1.70; 95% CI, 0.67-4.32). Screening uptake was higher in the intervention group (2618 participants [26.3%] vs 1719 participants [17.4%]; relative risk, 1.51; 95% CI, 1.43-1.60).

Conclusions and relevance: Mailing HPV kits to underscreened women increased screening uptake compared with usual care alone, with no significant differences in precancer detection or treatment. Results support the feasibility of mailing HPV kits to women who are overdue for screening as an outreach strategy to increase screening uptake in US health care systems. Efforts to increase kit uptake and follow-up of positive results are warranted to maximize detection and treatment of CIN2+.

Trial registration: ClinicalTrials.gov identifier: NCT02005510.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Winer reported receiving grants from the National Institutes of Health and Centers for Disease Control and Prevention outside the submitted work. Dr Tiro reported receiving grants from the National Institutes of Health, Lyda Hill Philanthropies, the Agency for Healthcare Research and Quality, and the Cancer Prevention & Research Institute of Texas outside the submitted work; as well as membership on the American Cancer Society's National HPV Vaccination Roundtable and attendance at St Jude's HPV Vaccine Strategy Workshop. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

We identified 63 789 women who were between the ages of 30 and 64 years, had not had a hysterectomy, had a primary care clinician at Kaiser Permanente Washington (KPWA), and had been continuously enrolled in the health system for at least 3 years and 5 months. Of these women, 17 256 (27.1%) had not had a Papanicolaou test within 3 years and 5 months. Postrandomization exclusions were applied owing to delays in data warehouse update. The total included in the intervention group analysis (9960) equals the total included in the round 1 analysis group (8120) plus the total included in the round 2 analysis group (1631) plus the total included in the round 3 analysis group (209). Similarly, the total included in the control group analysis (9891) equals the total included in the round 1 analysis group (8111) plus the total included in the round 2 analysis group (1585) plus the total included in the round 3 analysis group (195).

Figure 2.. Diagram of Cervical Cancer Screening, Diagnosis, and Treatment Outcomes

CIN2+ indicates positive results for cervical intraepithelial neoplasia grade 2 or higher; HPV, human papillomavirus; hrHPV, high-risk HPV; Unsat, unsatisfactory. aSelf-sampling other hrHPV+ only or unsatisfactory results required in-clinic follow-up to complete screening uptake. bOf these 20 women, 15 went directly to colposcopy and 5 went to Papanicolaou test or cotest before colposcopy. cThese 5 women completed screening uptake by receiving colposcopy in the 6 month screening window. dThis 1 woman did not complete screening uptake because colposcopy was completed outside the 6-month screening window. eIncludes 2 women with home kit other hrHPV+ and Papanicolaou test with unknown result. Because unknown Papanicolaou test results were coded as normal for analysis, the final result is considered other hrHPV+ and Papanicolaou test negative. One of these women received a colposcopy. fFollow-up recommendations were per national guidelines.

Figure 3.. Cumulative Incidence of Screening Uptake by Allocation and Screening Modality Within the Intervention Group