Mark H. Einstein

Supplementary Table S2 shows Systolic blood pressure of study participants at each visit, including immediately pre- and 30 minutes post-vaccination

Supplementary Table S4 shows respiratory rate of study participants at each visit, including immediately pre- and 30 minutes post-vaccination

Supplementary Table S5 shows the baseline blood counts and chemistry of study participants

Supplementary Table S1 shows Diastolic blood pressure of study participants at each study visit, including immediately pre- and 30 minutes post-vaccination

Supplementary Table S3 shows Heart rate of study participants at each visit, including immediately pre- and 30 minutes post-vaccination

Patients with human papillomavirus type 16 (HPV16) infection and low-grade cervical dysplasia [low-grade squamous intraepithelial lesion (LSIL)/CIN1] or atypical squamous cells [atypical squamous cells of undetermined significance (ASC-US)/atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion (ASC-H)] require active surveillance for disease progression. A safe and effective immunotherapy to clear HPV16 is an unmet medical need. The safety run-in cohort of a randomized double-blind, placebo-controlled phase II trial of PVX2 [vaccination twice with HPV16-targeting pNGVL4a-Sig/E7(detox)/HSP70 plasmid and once with the HPV16 L2E7E6 fusion protein “TA-CIN”] as immunotherapy for patients with HPV16+ ASC-US, ASC-H, or LSIL/CIN1 (NCT03911076) was recently completed. The primary objective of this cohort was to determine the safety and tolerability of PVX2 vaccination. Subjects were confirmed to have HPV16 infection and LSIL/CIN1, ASC-US, or ASC-H. Adverse events were evaluated using Common Terminology Criteria for Adverse Events v5.0. HPV typing by HPV16 18/45 Aptima Assay was done at baseline, month 6, and month 12, with simultaneous cytology analysis. Cervical biopsies and endocervical curettage were performed at baseline and month 6. In the safety run-in cohort 12 eligible patients were enrolled. Each received three monthly immunizations. One was lost to follow-up after week 12. There were no serious adverse events. A total of five adverse events were noted by 4 patients; 4 were considered not vaccine-related, and one ‘unlikely related’ by the investigator. At month 6, 45% (5/11) of participants converted to HPV16-negative and 2 others developed CIN2+ and received a loop electrosurgical excision procedure. At month 12, 64% (7/11) were HPV16-negative, including those HPV16-negative at month 6. In conclusion, PVX2 immunotherapy was well tolerated and associated with viral regression, supporting further testing.Prevention Relevance:This safety run-in study cohort suggests that PVX2 immunotherapy is well tolerated in the target population and is sufficiently safe to warrant further clinical testing in a randomized study. The combined vaccines may facilitate higher-than-expected rate of human papillomavirus type 16 viral clearance 6 and 12 months after treatment, although this requires validation.

Almost all cervical cancers are caused by human papillomaviruses (HPVs). In most cases, HPV DNA is integrated into the human genome. We found that tumor-specific, HPV-human DNA junctions are detectable in serum cell-free DNA of a fraction of cervical cancer patients at the time of initial treatment and/or at six months following treatment. Retrospective analysis revealed these junctions were more frequently detectable in women in whom the cancer later recurred. We also found that cervical cancers caused by HPV types outside of phylogenetic clade α9 had a higher recurrence frequency than those caused by α9 types in both our study and The Cancer Genome Atlas cervical cancer database, despite the higher prevalence of α9 types including HPV16 in cervical cancer. Thus, HPV-human DNA junction detection in serum cell-free DNA and HPV type determination in tumor tissue may help predict recurrence risk. Screening serum cell-free DNA for junctions may also offer an unambiguous, non-invasive means to monitor absence of recurrence following treatment.

Background: Cervical cancer disparities persist among minoritized women due to infrequent screening and poor follow-up. Structural and psychosocial barriers to following up with colposcopy are problematic for minoritized women. Evidence-based interventions using patient navigation and tailored telephone counseling, including the Tailored Communication for Cervical Cancer Risk (TC3), have modestly improved colposcopy attendance. However, the efficacious TC3 intervention is human resource-intense and could have greater reach if adapted for mobile health, which increases convenience and access to health information. Objective: This study aimed to describe feedback from clinic staff members involved in colposcopy processes and patients referred for colposcopy regarding adaptions to the TC3 phone-based intervention to text messaging, which addresses barriers among those referred for colposcopy after abnormal screening results. Methods: Semistructured depth qualitative interviews were conducted over Zoom [Zoom Communications, Inc] or telephone with a purposive sample of 22 clinic staff members (including clinicians and support staff members) and 34 patients referred for colposcopy from 3 academic obstetrics and gynecology (OB-GYN) clinics that serve predominantly low-income, minoritized patients in different urban locations in New Jersey and Pennsylvania. Participants were asked about colposcopy attendance barriers and perspectives on a proposed text message intervention to provide tailored education and support in the time between abnormal cervical screening and colposcopy. The analytic team discussed interviews, wrote summaries, and consensus-coded transcripts, analyzing output for emergent findings and crystallizing themes. Results: Clinic staff members and patients had mixed feelings about a text-only intervention. They overwhelmingly perceived a need to provide patients with appointment reminders and information about abnormal cervical screening results and colposcopy purpose and procedure. Both groups also thought messages emphasizing that human papillomavirus is common and cervical cancer can be prevented with follow-up could enhance attendance. However, some had concerns about the privacy of text messages and text fatigue. Both groups thought that talking to clinic staff members was needed in certain instances; they proposed connecting patients experiencing complex psychosocial or structural barriers to staff members for additional information, psychological support, and help with scheduling around work and finding childcare and transportation solutions. They also identified inadequate scheduling and reminder systems as barriers. From this feedback, we revised our text message content and intervention design, adding a health coaching component to support patients with complex barriers and concerns. Conclusions: Clinic staff members and patient perspectives are critical for designing appropriate and relevant interventions. These groups conveyed that text message-only interventions may be useful for patients with lesser barriers who may benefit from reminders, basic educational information, and scheduling support. However, multimodal interventions may be necessary for patients with complex barriers to colposcopy attendance, which we intend to evaluate in a subsequent trial.

Almost all cervical cancers are caused by human papillomaviruses (HPVs). In most cases, HPV DNA is integrated into the human genome. We found that tumor-specific, HPV-human DNA junctions are detectable in serum cell-free DNA of a fraction of cervical cancer patients at the time of initial treatment and/or at six months following treatment. Retrospective analysis revealed these junctions were more frequently detectable in women in whom the cancer later recurred. We also found that cervical cancers caused by HPV types outside of phylogenetic clade α9 had a higher recurrence frequency than those caused by α9 types in both our study and The Cancer Genome Atlas cervical cancer database, despite the higher prevalence of α9 types including HPV16 in cervical cancer. Thus, HPV-human DNA junction detection in serum cell-free DNA and HPV type determination in tumor tissue may help predict recurrence risk. Screening serum cell-free DNA for junctions may also offer an unambiguous, non-invasive means to monitor absence of recurrence following treatment.

BACKGROUND Cervical cancer disparities persist among minoritized women due to infrequent screening and poor follow-up. Structural and psychosocial barriers to following up with colposcopy are problematic for minoritized women. Evidence-based interventions using patient navigation and tailored telephone counseling, including the Tailored Communication for Cervical Cancer Risk (TC3), have modestly improved colposcopy attendance. However, the efficacious TC3 intervention is human resource-intense and could have greater reach if adapted for mobile health, which increases convenience and access to health information. OBJECTIVE This study aimed to describe feedback from clinic staff members involved in colposcopy processes and patients referred for colposcopy regarding adaptions to the TC3 phone-based intervention to text messaging, which addresses barriers among those referred for colposcopy after abnormal screening results. METHODS Semistructured depth qualitative interviews were conducted over Zoom [Zoom Communications, Inc] or telephone with a purposive sample of 22 clinic staff members (including clinicians and support staff members) and 34 patients referred for colposcopy from 3 academic obstetrics and gynecology (OB-GYN) clinics that serve predominantly low-income, minoritized patients in different urban locations in New Jersey and Pennsylvania. Participants were asked about colposcopy attendance barriers and perspectives on a proposed text message intervention to provide tailored education and support in the time between abnormal cervical screening and colposcopy. The analytic team discussed interviews, wrote summaries, and consensus-coded transcripts, analyzing output for emergent findings and crystallizing themes. RESULTS Clinic staff members and patients had mixed feelings about a text-only intervention. They overwhelmingly perceived a need to provide patients with appointment reminders and information about abnormal cervical screening results and colposcopy purpose and procedure. Both groups also thought messages emphasizing that human papillomavirus is common and cervical cancer can be prevented with follow-up could enhance attendance. However, some had concerns about the privacy of text messages and text fatigue. Both groups thought that talking to clinic staff members was needed in certain instances; they proposed connecting patients experiencing complex psychosocial or structural barriers to staff members for additional information, psychological support, and help with scheduling around work and finding childcare and transportation solutions. They also identified inadequate scheduling and reminder systems as barriers. From this feedback, we revised our text message content and intervention design, adding a health coaching component to support patients with complex barriers and concerns. CONCLUSIONS Clinic staff members and patient perspectives are critical for designing appropriate and relevant interventions. These groups conveyed that text message-only interventions may be useful for patients with lesser barriers who may benefit from reminders, basic educational information, and scheduling support. However, multimodal interventions may be necessary for patients with complex barriers to colposcopy attendance, which we intend to evaluate in a subsequent trial. CLINICALTRIAL