John Lin

A Pooled Analysis to Compare the Clinical Characteristics of Human Papillomavirus–positive and -Negative Cervical Precancers

Abstract Given that high-risk human papillomavirus (HPV) is the necessary cause of virtually all cervical cancer, the clinical meaning of HPV-negative cervical precancer is unknown. We, therefore, conducted a literature search in Ovid MEDLINE, PubMed Central, and Google Scholar to identify English-language studies in which (i) HPV-negative and -positive, histologically confirmed cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) were detected and (ii) summarized statistics or deidentified individual data were available to summarize proportions of biomarkers indicating risk of cancer. Nineteen studies including 3,089 (91.0%) HPV-positive and 307 (9.0%) HPV-negative CIN2+ were analyzed. HPV-positive CIN2+ (vs. HPV-negative CIN2+) was more likely to test positive for biomarkers linked to cancer risk: a study diagnosis of CIN3+ (vs. CIN2; 18 studies; 0.56 vs. 0.24; P < 0.001) preceding high-grade squamous intraepithelial lesion cytology (15 studies; 0.54 vs. 0.10; P < 0.001); and high-grade colposcopic impression (13 studies; 0.30 vs. 0.18; P = 0.03). HPV-negative CIN2+ was more likely to test positive for low-risk HPV genotypes than HPV-positive CIN2+ (P < 0.001). HPV-negative CIN2+ appears to have lower cancer risk than HPV-positive CIN2+. Clinical studies of human high-risk HPV testing for screening to prevent cervical cancer may refer samples of HPV test–negative women for disease ascertainment to correct verification bias in the estimates of clinical performance. However, verification bias adjustment of the clinical performance of HPV testing may overcorrect/underestimate its clinical performance to detect truly precancerous abnormalities.

Promoting cervical cancer screening via a mailed HPV self-collection kit: Reactions from screeners and non-screeners.

Mailed human papillomavirus self-collection (HPV-SC) kits improve cervical cancer screening adherence; however, not all respond to kit invitations. This qualitative study sought to understand reactions to HPV-SC kit invitation among screeners and non-screeners in the STEP trial, a pragmatic trial offering kits. Kaiser Permanente Washington patients randomized to the STEP trial's kit intervention arms, received educational materials and were notified they would receive a kit in one week (direct mail) or given information on how to request a kit (opt-in). Materials highlighted cancer risk, screening importance, test differences (Pap, HPV), and what to expect with abnormal results. Based on their screening status 6 months post-randomization, two categories of patients were invited for focus groups: 1) screeners with negative kit results or clinician-performed test; 2) non-screeners. We oversampled non-white patients. Six online focus groups were conducted from May to June 2022 with 40 patients (29 screeners, 11 non-screeners). A facilitator asked about HPV and cervical cancer knowledge, reaction to the kit and educational materials, and screening preference (self- vs. clinician-collected). Field notes and transcripts were analyzed by five coders using iterative content analysis. Participants desired more flexibility during the invitation process, preferring multiple methods (mail, patient portal, text, in-clinic distribution) and support services (website, nurse-staffed phone). Educational resources acknowledging different learning styles (print, diagrams, audio-visual) and for specific populations (LGBTQ, monogamous) were suggested. Participants recommended clinicians reinforce kit efficacy to encourage use. Trust in the kit and in the health care system were key to ensure comfort with self-collection. Multiple, diverse outreach strategies are needed to engage patients in screening with this new modality. Flexible engagement by the healthcare system with comprehensive educational materials inclusive of diverse populations, and provider encouragement are needed to build patients' trust in, comfort with, and use of HPV-SC tests. ClinicalTrials.gov Identifier: NCT04679675.