SUMMARY Clinic-based screening for cervical cancer has dramatically reduced the incidence of this disease in the U.S. and other countries with widespread screening programs. However, almost 20% of U.S. women remain at high risk for cervical cancer due to non- and under-participation in screening. Testing self-collected cervicovaginal samples for high-risk human papillomavirus (HR-HPV) is known to be an effective strategy for addressing barriers to clinic-based screening in global settings. However, there are limited data on its effectiveness and implementation in U.S. health systems, particularly in safety net health systems that serve socioeconomically disadvantaged minority populations who carry the highest burden of cervical cancer. In the context of safety net health systems, pairing mailed self-sample HPV testing with patient navigation, an evidence-based outreach intervention, may have a synergistic effect for increasing screening participation among underscreened women. The Prospective Evaluation of Self-Testing to Increase Screening (PRESTIS) trial is the first trial to evaluate mailed self-sample HPV testing in U.S. safety net health settings. The patient population of the safety net health system where the PRESTIS trial is embedded is predominantly Hispanic and non-Hispanic Black. Reflecting this demographic composition and logistical constraints of implementing the trial, eligibility is currently limited to patients who speak English or Spanish. Asian/Asian American women who speak English currently comprise a small proportion of trial participants (4%). Furthermore, Asian/Asian American women who speak languages other than English (particularly Vietnamese, the primary language of 68% of Asian patients) are currently ineligible for the trial. The small number of Asian/Asian American patients in the trial is problematic as it precludes their inclusion in subgroup analyses and limits the generalizeability of trial findings. The inclusion of Asian/Asian American women in self-sampling trials is critical given that cervical cancer screening participation is low among Asian/Asian American women and certain Asian subpopulations, notably Vietnamese women, have higher cervical cancer incidence compared to women of other race/ethnicities. With the proposed Administrative Supplement, we will expand the PRESTIS trial by adapting patient education materials and navigation strategies to broaden the trial’s population and recruit Asian/Asian American women who are not up-to-date with cervical cancer screening. In doing so, we will ensure that the PRESTIS trial is powered to rigorously assess and compare screening participation across racial/ethnic and linguistic subpopulations inclusive of Asian/Asian American women. We will also assess acceptability and experiences with self-sampling among Asian/Asian American women, as well as barriers and facilitators to clinical follow-up among Asian/Asian American women who test positive for HR-HPV.