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Invited Commentary
Obstetrics and Gynecology
November 6, 2019

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

Author Affiliations
  • 1Department of Obstetrics and Gynecology, John Hopkins University, Baltimore, Maryland
JAMA Netw Open. 2019;2(11):e1914704. doi:10.1001/jamanetworkopen.2019.14704

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.

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Article Information

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.

References
1.
Winer  RL, Lin  J, Tiro  JA,  et al.  Effect of mailed human papillomavirus test kits vs usual care reminders on cervical cancer screening uptake, precancer detection, and treatment: a randomized clinical trial.  JAMA Netw Open. 2019;2(11):e1914729. doi:10.1001/jamanetworkopen.2019.14729Google Scholar
2.
Kulasingam  SL, Hughes  JP, Kiviat  NB,  et al.  Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of referral.  JAMA. 2002;288(14):1749-1757. doi:10.1001/jama.288.14.1749PubMedGoogle ScholarCrossref
3.
Datta  SD, Koutsky  LA, Ratelle  S,  et al.  Human papillomavirus infection and cervical cytology in women screened for cervical cancer in the United States, 2003-2005.  Ann Intern Med. 2008;148(7):493-500. doi:10.7326/0003-4819-148-7-200804010-00004PubMedGoogle ScholarCrossref
4.
Ward  E, Jemal  A, Cokkinides  V,  et al.  Cancer disparities by race/ethnicity and socioeconomic status.  CA Cancer J Clin. 2004;54(2):78-93. doi:10.3322/canjclin.54.2.78PubMedGoogle ScholarCrossref
5.
Wang  X, Fang  C, Tan  Y, Liu  A, Ma  GX.  Evidence-based intervention to reduce access barriers to cervical cancer screening among underserved Chinese American women.  J Womens Health (Larchmt). 2010;19(3):463-469. doi:10.1089/jwh.2009.1422PubMedGoogle ScholarCrossref
6.
Castle  PE, Rausa  A, Walls  T,  et al.  Comparative community outreach to increase cervical cancer screening in the Mississippi Delta.  Prev Med. 2011;52(6):452-455. doi:10.1016/j.ypmed.2011.03.018PubMedGoogle ScholarCrossref
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    1 Comment for this article
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    Authors' Reply
    Rachel Winer, PhD, MPH | University of Washington
    We would like to clarify two points raised by Moss et al.(1) in their thoughtful commentary.

    First, the authors suggest that some of the HOME(2) trial participants may not have been overdue for screening if they were on a 5-year versus 3-year routine screening schedule. A 5-year screening interval is recommended for women who screen negative on a Papanicolaou/HPV co-test.(3) However, co-testing was not standard of care at Kaiser Permanente Washington until August 2013, and HOME enrolled participants from February 2014 through August 2016. Given this timing, women who were co-tested on or after August 2013 could not
    have met the HOME eligibility criterion of no Papanicolaou test within 3 years plus 5 months. For example, a woman who received a co-test in August 2013 and was assessed for HOME trial eligibility in August 2016 would have only accrued 3 years without screening.

    Second, Moss et al.(1) suggest low HPV test positivity may have contributed to the non-significant difference in CIN2+ detection between arms. HPV positivity in home kits (11.3%) was actually higher than assumed in trial power calculations (7.5%), and consistent with international trials in similarly-aged unscreened women (11% in a recent meta-analysis [4]). The authors note that high-risk HPV prevalence may be as high as 35%, citing an earlier study of women in 26 sexually transmitted disease, family planning, and primary care clinics.(5) In that study, 35% prevalence was observed in females aged 14-19 years – below the recommended age for initiating cervical cancer screening, and well below the recommended age range for primary screening strategies that incorporate HPV testing (either alone or in combination with Papanicolaou testing). In that same study, high-risk HPV prevalence was 13%, 11%, and 6% in women aged 30-39, 40-49, and 50-65 years, respectively.

    We agree with Moss et al.(1) that our findings support home HPV testing as a feasible screening option with potential to increase access to cervical cancer screening.

    Rachel L. Winer, PhD, MPH
    John Lin, BA
    Diana S.M. Buist, PhD, MPH


    1. Moss CF, Chou B, Coleman JS. Home screening for human papillomavirus falls short in initial application, remains promising. JAMA Netw Open. 2019;2(11):e1914704. doi:10.1001/jamanetworkopen.2019.14704

    2. Winer RL, Lin J, Tiro JA, et al. Effect of mailed human papillomavirus test kits vs usual care reminders on cervical cancer screening uptake, precancer detection, and treatment: a randomized clinical trial. JAMA Netw Open. 2019;2(11):e1914729. doi:10.1001/jamanetworkopen.2019.14729

    3. Curry SJ, Krist AH, Owens DK, et al; US Preventive Services Task Force. Screening for cervical cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(7):674-686. doi:10.1001/jama.2018.10897

    4. Arbyn M, Smith SB, Temin S, Sultana F, Castle P; Collaboration on Self-Sampling and HPV Testing. Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses. BMJ. 2018;363:k4823. doi:10.1136/bmj.k4823

    5. Datta SD, Koutsky LA, Ratelle S, et al. Human papillomavirus infection and cervical cytology in women screened for cervical cancer in the United States, 2003-2005. Ann Intern Med. 2008;148(7):493-500. doi:10.7326/0003-4819-148-7-200804010-00004
    CONFLICT OF INTEREST: None Reported
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