Home Screening for Human Papillomavirus Falls Short in Initial Application, Remains Promising

In their randomized clinical trial, Winer et al¹ studied the effect of mailed human papillomavirus (HPV) self-screening kits vs usual care reminders on cervical cancer screening among underscreened women (ie, women whose last Papanicolaou test was more than 3.4 years before the intervention) in the Kaiser Permanente health care system. As the authors note,¹ the challenges of increasing cervical cancer screening uptake are daunting, and overcoming those challenges has the potential to drastically reduce morbidity and mortality from cervical cancer. Given the barriers to in-clinic screening, the idea of home HPV testing to increase cancer prevention efforts is appealing. Although the intervention did not lead to a statistically significant increase in the primary outcomes of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) detection (relative risk, 1.49; 95% CI, 0.61-3.64) or treatment (relative risk, 1.70; 95% CI, 0.67-4.32), the intervention increased screening uptake (relative risk, 1.51; 95% CI, 1.43-1.60) and reduced the time to screening uptake (median [interquartile range] time to screening uptake: 37 [22-49] days vs 80 [43-129] days).¹ While the trial is admirable in its design and large sample size, several limitations prevent it from having broad implications for cervical cancer screening at this time.

Of 9960 women in the intervention group, only 1206 (12.1%) returned the kit,¹ which may have been due to several factors. First, patients were instructed to undergo clinic-based screening regardless of home HPV screening; thus, motivation to use the kit may have been low. Second, some patients may have been aware that they were not due for screening based on American Society for Colposcopy and Cervical Pathology guidelines. Kits were mailed to patients slightly more than 3 years after their last screening, and patients older than 30 years with previous negative cotesting (ie, normal Papanicolaou cytology and negative HPV testing) would have almost 2 years before their next recommended screening was due. Third, patients may have been wary of home screening given that vaginal HPV testing is not approved by the US Food and Drug Administration for risk stratification in cervical cancer screening. Furthermore, patients may have lacked knowledge regarding the superior sensitivity and negative predictive value of HPV testing.² It is understandable given these factors that the effect of this mailed HPV kit on screening uptake was modest, with an increase of only 8.9% (95% CI, 7.8%-10.0%) over usual care.¹

Despite an increase in screening uptake, the primary outcome of detected or treated CIN2+ was not significantly different among those who received the HPV kit than among those who underwent usual care reminders. This may be partly because of low prevalence of dysplasia in this population. The study population had low HPV test positivity (12%) compared with more diverse clinic settings and age ranges, in which high-risk HPV may be as prevalent as 35%.³ It is especially concerning that slightly less than half of patients (41%) who had positive test results for HPV-16 or HPV-18 did not adhere to the recommended colposcopy.¹ This percentage may have been further diminished by the 6-month limitation on measurement of follow-up for enrolled patients.

The selected population had several characteristics that may further limit broad application of the trial findings, and thus, we do not think the limited kit return or CIN 2+ detection should discount the promise of self-screening generally. Enrolled patients had stable health insurance, were English speaking, had a mean age older than 50 years, and were under the care of a primary care practitioner for a long duration before contact by the study team. In other settings, underscreened women may be without primary care and insurance⁴ or without a stable address at which to receive a mailed kit. Targeted interventions by community health workers have been shown to improve screening uptake in such patients⁵; extension of this intervention with kit distribution is feasible and may significantly improve uptake, as shown in at least 1 small trial.⁶ Thus, a larger self-swab program in places of opportunistic contact (ie, shelters, health caravans, or health fairs targeting high-risk populations) may more significantly increase screening uptake and subsequent treatment of dysplasia because of the immense barriers to clinic appointment attendance that a home-kit distribution could overcome for such patients. Additionally, the higher prevalence of dysplasia in socioeconomically disadvantaged populations may make clinical outcome differences detectable even with a low percentage of kits returned. Our optimism coexists with the caveat that such patients are also likely to have significant barriers to colposcopy even if their screen is positive for high-risk HPV subtypes, as demonstrated in the low-risk population in the trial conducted by Winer et al.¹

Overall, this impressive randomized clinical trial demonstrated that implementation of a home HPV screening program is feasible for large health care systems. The strategy especially merits further research in populations with lower resources and higher disease prevalence. With the high negative predictive value of HPV testing and expected decline in CIN2+ with HPV vaccination, home HPV screening may also be more useful for future screening among populations with stable access to health resources, such as those in the present study. Of course, home HPV testing can only be part of the solution to cervical cancer prevention and should be implemented in tandem with continued prevention strategies, such as HPV vaccination administration in all populations.

Published: November 6, 2019. doi:10.1001/jamanetworkopen.2019.14704

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Moss CF et al. JAMA Network Open.

Corresponding Author: Jenell S. Coleman, MD, MPH, Johns Hopkins University, 600 N Wolfe St, Phipps Bldg Room 257B, Baltimore, MD 21287 (colemanj@jhmi.edu).

Conflict of Interest Disclosures: None reported.