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Background: Mailing HPV self-sampling kits to overdue individuals increases cervical cancer screening adherence; offering self-sampling to previously adherent individuals has not been evaluated in the U.S. Given heterogeneity of the U.S. health system and population, data are needed to optimize how HPV self-sampling is offered to individuals who are overdue, due after successful past screening, or have an unknown screening history., Methods: STEP is a pragmatic randomized controlled trial set within a U.S. integrated healthcare delivery system, designed to compare different outreach approaches for offering HPV self-sampling in populations defined by prior screening behavior (previously-adherent, overdue, or unknown screening history). Over 14 months, eligible individuals were identified through electronic medical record (EMR) data and randomized to Usual Care (UC), Education (UC + educational materials about cervical cancer screening), Direct-Mail (UC + Education + a mailed self-sampling kit) or Opt-In (UC + Education + option to request a kit), depending on screening history. The primary objective is to compare screening completion by outreach approach and screening history. Secondary objectives include evaluating incremental cost-effectiveness of outreach approaches, and identifying patient preference for, and satisfaction with, HPV self-screening, and barriers to abnormal results follow-up (measured through interviews and focus groups)., Conclusions: The trial was designed to generate data that U.S. health systems can use to inform primary HPV screening implementation strategies that incorporate HPV self-sampling options to improve screening access, adherence, and patient satisfaction. The objective of this report is to describe the rationale and design of this pragmatic trial., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Mailing human papillomavirus (HPV) self-sampling kits increases cervical cancer screening participation, but effects may differ across subpopulations. Subpopulation data can inform US health care system implementation., Objective: To identify patient characteristics that modify effectiveness of a mailed kit intervention at increasing screening., Design, Setting, and Participants: This was a secondary analysis of data from the Home-Based Options to Make Cervical Cancer Screening Easy (HOME) randomized clinical trial conducted from 2014 to 2018 at Kaiser Permanente Washington. Data analysis was performed from March 2018 to May 2022. Individuals aged 30 to 64 years with female sex, health plan enrollment longer than 3 years and 5 months, a current primary care clinician, and no Papanicolaou test within the prior 3 years and 5 months were identified through electronic medical records and randomized (1:1) to the control or intervention group., Interventions: The control group received usual care Papanicolaou screening reminders and outreach. The intervention group received usual care plus an unsolicited mailed HPV self-sampling kit., Main Outcomes and Measures: Screening uptake was captured within 6 months after randomization. Baseline patient characteristics (age, race, ethnicity, travel time to clinic, income, body mass index, tobacco use, health plan enrollment duration, time since last Papanicolaou test, mammography, comorbidities, and colorectal cancer screening adherence) were extracted from the electronic medical record., Results: Of 19 734 individuals (mean [SD] age, 50.1 [9.5] years; 14 129 [71.6%] White), 9843 were randomized to the intervention group, and 9891 were randomized to the control group. Screening uptake was 26.3% (2592 of 9843 individuals) in the intervention group vs 17.4% (1719 of 9891 individuals) in the control group (relative risk [RR], 1.51; 95% CI, 1.43-1.60). Although absolute differences in uptake by group varied little by screening history, relative effects were greater with longer vs shorter time since last Papanicolaou test (no prior Papanicolaou test: RRs, 1.85-3.25; ≥10 years: RR, 2.78; 5-10 years: RRs, 1.69-1.86; <5 years: RRs 1.29-1.37). Relative effects were greater in participants overdue (RR, 2.03; 95% CI, 1.73-2.38) vs up-to-date with mammography (RR, 1.53; 95% CI, 1.41-1.67), although absolute difference was greater in the up-to-date group. Differences by age were not significant, with RRs of 1.33 to 1.48 across 5-year age groups in participants 30 to 54, vs 1.60 (95% CI, 1.40-1.82) in participants 55 to 59 and 1.77 (95% CI, 1.56-2.01) in participants 60 to 64 years. Among those mailed kits, there were differences in kit use vs in-clinic screening by age, race, plan enrollment duration, underscreening duration, and colorectal cancer screening adherence., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, clinically important improvements in screening uptake were observed for all subgroups. Differences in magnitude of intervention effect and kit use highlighted opportunities to optimize HPV self-sampling for priority groups., Trial Registration: ClinicalTrials.gov Identifier: NCT02005510.

Background: In the United States, human papillomavirus (HPV) vaccination has been recommended since 2011 for boys aged 11-12 years, with catch-up vaccination recommended through age 26 years for previously unvaccinated men who have sex with men (MSM)., Methods: During 2016-2018, a cross-sectional study enrolled MSM and transgender women aged 18-26 years in Seattle, Washington. Participants submitted self-collected penile swab specimens for HPV genotyping. HPV vaccination history was self-reported. We compared HPV prevalence among vaccinated participants with that in participants with no or unknown vaccination history, using log-binomial regression to estimate adjusted prevalence ratios and confidence intervals., Results: Among 687 participants, 348 (50.7%) self-reported ever receiving ≥1 HPV vaccine dose; the median age at first HPV vaccination was 21 years, and the median age at first sex, 17 years. Overall, the prevalence of penile quadrivalent HPV vaccine (4vHPV)-type HPV was similar in vaccinated participants (12.1%) and participants with no or unknown vaccination (15.6%) (adjusted prevalence ratio, 0.69 [95% confidence interval, .47-1.01]). However, the prevalence was significantly lower in participants vaccinated at age ≤18 years than in those with no of unknown vaccination (0.15 [.04-.62]), corresponding to a vaccine effectiveness of 85% against 4vHPV-type HPV., Conclusions: Results suggest that HPV vaccination is effective in preventing penile HPV infections in young MSM when administered at age ≤18 years., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: Vaccine-preventable human papillomavirus (HPV) infection is common, especially in sub-Saharan Africa where HIV risk is also high. However, unlike other sexually transmitted infections (STIs), HPV's role in HIV acquisition is unclear. We evaluated this relationship using data from MTN-003, a clinical trial of HIV chemoprophylaxis among cisgender women in sub-Saharan Africa., Design: A case-control study., Methods: We matched 138 women who acquired HIV (cases) to 412 HIV-negative controls. Cervicovaginal swabs collected within 6 months before HIV seroconversion were tested for HPV DNA. We estimated the associations between carcinogenic (high-risk) and low-risk HPV types and types targeted by HPV vaccines and HIV acquisition, using conditional logistic regression models adjusted for time-varying sexual behaviors and other STIs., Results: Mean age was 23 (±4) years. Any, high-risk and low-risk HPV was detected in 84, 74 and 66% of cases, and 65, 55 and 48% of controls. Infection with at least two HPV types was common in cases (67%) and controls (49%), as was infection with nonavalent vaccine-targeted types (60 and 42%). HIV acquisition increased with any [adjusted odds ratio (aOR) 2.5, 95% confidence interval (95% CI) 1.3-4.7], high-risk (aOR 2.6, 95% CI 1.5-4.6) and low-risk (aOR 1.8, 95% CI 1.1-2.9) HPV. Each additional type detected increased HIV risk by 20% (aOR 1.2, 95% CI 1.1-1.4). HIV acquisition was associated with HPV types targeted by the nonavalent (aOR 2.1, 95% CI 1.3-3.6) and quadrivalent vaccines (aOR 1.9, 95% CI 1.1-3.2)., Conclusion: HPV infection is associated with HIV acquisition in sub-Saharan African women. In addition to preventing HPV-associated cancers, increasing HPV vaccination coverage could potentially reduce HIV incidence., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Women overdue for cervical cancer screening often have other preventive care gaps. We examined whether mailing unsolicited human papillomavirus (HPV) self-sampling kits to increase cervical cancer screening impacted receipt of other preventive services women were due for: mammography, colorectal cancer (CRC) screening, influenza vaccination, depression screening, and diabetic HbA1c monitoring. From 2014 to 2016, 16,590 underscreened women were randomized to receive a mailed kit or usual care Pap reminders within Kaiser Permanente Washington. We used logistic regression to estimate odds ratios (ORs) of preventive services receipt within 12-months between the intervention vs. control arms, and within the intervention arm (comparing those returning a kit vs. attending Pap vs. nothing), adjusting models for demographic variables. There were no significant between-arm differences in uptake of any of the preventive services: intervention vs. control: mammography OR = 1.01 (95% confidence interval:0.88-1.17), CRC screening OR = 0.98 (0.86-1.13), influenza vaccination OR = 0.99 (0.92-1.06), depression screening OR = 1.07 (0.99-1.16), HbA1c OR = 0.84 (0.62-1.13). Within the intervention arm, preventive services uptake was higher in women who completed cervical cancer screening vs. did not, with stronger effects for women who attended Pap: Pap vs. nothing: mammography OR = 11.81 (8.11-17.19), CRC screening OR = 7.31 (5.57-9.58), influenza vaccination OR = 2.06 (1.82-2.32), depression screening OR = 1.79 (1.57-2.05), HbA1c OR = 3.35 (1.49-7.52); kit vs. nothing: mammography OR = 2.26 (1.56-3.26), CRC screening OR = 5.05 (3.57-7.14), influenza vaccination OR = 1.67 (1.41-1.98), depression screening OR = 1.09 (0.89-1.33), HbA1c OR = 1.23 (0.57-2.65). Mailing HPV self-sampling kits to underscreened women did not negatively impact uptake of other preventive services. However, overall preventive service uptake was the highest among women who attended in-clinic cervical cancer screening., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: We assessed the sensitivity of self-reported human papillomavirus (HPV) vaccination among young adult men who have sex with men (MSM) with documented HPV vaccination., Methods: During 2016-2018, MSM and transgender women aged 18 to 26 years were enrolled in Seattle, WA. A history of HPV vaccination was assessed via self-administered survey, clinic electronic medical records, and the Washington State Immunization Information System. We assessed self-report sensitivity among participants with documented prior HPV vaccination (≥1 dose) in either the electronic medical record or the Washington State Immunization Information System, and used logistic regression to compare sensitivity by age, number of doses, and time since first dose., Results: Of 292 participants with ≥1 documented HPV vaccine dose, 243 self-reported ≥1 dose (sensitivity, 83.2%; 95% confidence interval [CI], 78.4%-87.3%). Compared with participants whose first dose was <1 year ago, the likelihood of self-report was lower among those with ≥3 years since first dose (adjusted odds ratio [aOR], 0.2; 95% CI, 0.1-0.5). Furthermore, compared with participants with only 1 documented HPV vaccine dose, the likelihood of self-reporting ≥1 dose was higher among those with 2 (aOR, 2.4; 95% CI, 1.0-5.5) or ≥3 doses (aOR, 6.2; 95% CI, 2.7-14.4). Among 115 participants with ≥3 documented doses, sensitivity for recalling ≥3 doses was 69.6% (95% CI, 60.3%-77.8%)., Conclusions: Most young adult MSM with a documented history of HPV vaccination self-reported prior HPV vaccination. Although recall was highest in those with ≥3 doses, 30% of this fully vaccinated subgroup did not correctly recall the number of doses received, highlighting limitations of self-reporting. Furthermore, results indicating reduced recall with ≥3 years since first dose suggest that sensitivity of self-report among young adult MSM may decline over time as adolescent vaccination coverage increases., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no financial or other substantive conflict of interest or disclosures. This journal article is a product of a Prevention Research Center and was supported by Cooperative Agreement Number U48 DP005013-02S7 from the Centers for Disease Control and Prevention., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Gay, bisexual, and other men who have sex with men (MSM) and transgender women are disproportionately affected by human papillomavirus (HPV). HPV vaccination is routinely recommended for U.S. adolescents at age 11-12 years, with catch-up vaccination through age 26 years. We assessed HPV vaccination coverage and associated factors among young MSM and transgender women. The Vaccine Impact in Men study enrolled MSM aged 18-26 years from clinics in Seattle, Chicago, and Los Angeles, during February 2016-September 2018. Participants self-reported socio-demographic information and HPV vaccination status. Among 1416 participants, 673 (47.5%) reported ≥1 HPV vaccine dose. Among vaccinated participants, median age at first dose was 19 years and median age at first sex was 17 years; 493 (73.3%) reported that their age at first dose was older than their age at first sex. There were significant differences in HPV vaccination coverage by city (range 33%-62%), age, race/ethnicity, and gender identity. Coverage was highest in Seattle, where younger age was the only factor associated with vaccination. Differences in coverage by city may be due to variation in vaccination practices or enrollment at study sites. Increasing both routine and catch-up vaccination will improve coverage among MSM and transgender women.

Cervical cancer is the fourth-leading cause of cancer deaths among women worldwide and most cases occur in developing countries. Detection of high-risk (HR) HPV, the etiologic agent of cervical cancer, is a primary screening method for cervical cancer. However, the current gold standard for HPV detection, real-time PCR, is expensive, time-consuming, and instrumentation-intensive. A rapid, low-cost HPV detection method is needed for cervical cancer screening in low-resource settings. We previously developed a digital loop-mediated isothermal amplification (dLAMP) assay for rapid, quantitative detection of nucleic acids without the need for thermocycling. This assay employs a microfluidic self-digitization chip to automatically digitize a sample into an array of nanoliter wells in a simple assay format. Here we evaluate the dLAMP assay and self-digitization chip for detection of the commonly tested 14 high-risk HPVs in clinical samples. The dLAMP platform provided reliable genotyping and quantitative detection of the 14 high-risk HPVs with high sensitivity, demonstrating its potential for simple, rapid, and low-cost diagnosis of HPV infection.

Objectives: To evaluate experiences and reactions after receiving a mailed, unsolicited human papillomavirus self-sampling kit and identify psychosocial correlates of using kits., Methods: Survey participants were underscreened women aged 30-64 who were mailed human papillomavirus kits as part of a pragmatic trial at Kaiser Permanente Washington, a United States integrated health care system. Six months after the mailing, we invited kit returners and non-returners to complete a web survey that measured psychosocial factors (e.g. cervical cancer/human papillomavirus knowledge, attitudes toward screening), experiences, and reactions to kits. We compared responses between kit returners and non-returners., Results: Comparing 116 kit returners (272 invited) and 119 non-returners (1083 invited), we found no clinically significant differences in psychosocial factors. Overall, survey respondents showed knowledge gaps in human papillomavirus natural history (82% did not know human papillomavirus infection can clear on its own) and interpreting human papillomavirus test results (37% did not know a human papillomavirus-negative result indicates low cancer risk). Kit returners found kits convenient and easy to use (>90%). The most common reason for non-return was low confidence in ability to correctly use a kit, although many non-returners (49%) indicated that they would consider future use. Women reported low trust in human papillomavirus testing to identify women at high risk for cervical cancer (52% in returners, 42% in non-returners)., Conclusions: Screening programs could improve uptake and acceptability of human papillomavirus self-sampling through outreach materials that emphasize the high efficacy of human papillomavirus testing for cervical cancer screening and educate patients about how to interpret results.

Background: Data on clinical outcomes of infection with variants of oncogenic human papillomavirus (HPV) types other than HPV16 and HPV18 are rare. We investigated intratypic variations in non-HPV16/18 oncogenic types and their corresponding relationships with cervical intraepithelial neoplasia grades 2-3 (CIN2/3)., Methods: Study subjects were women who were positive for one or more of 11 non-HPV16/18 oncogenic types. Subjects were followed every six months for two years for detection of HPV and cervical lesions. Variant lineages were defined by sequencing the 3' part of the long control region and the entire E6/E7 region of HPV genome. Lineage-associated risk of CIN2/3 was assessed using logistic regression with generalized estimating equations., Results: A total of 4591 type-specific HPV infections among 2667 women were included in the analysis. The increase in risk of CIN2/3 was statistically significant for women with HPV31 A or B compared with C variants, HPV33 A1 compared with B variants, HPV45 A3 or B2 compared with B1 variants, HPV56 B compared with A2 variants, and HPV58 A1 or A3 compared with C variants. For these five types, the adjusted odds ratio associated with CIN2/3 was 2.0 (95% confidence interval [CI] = 1.5 to 2.6) for infections with single-type high-risk (HR) variants, 1.7 (95% CI = 1.0 to 2.7) for infections with two or more types but only one HR variant, and 5.3 (95% CI = 3.1 to 8.4) for infections with HR variants of two or more types as compared with those with single-type non-HR variants. The likelihood of CIN2/3 was similar for women with HPV16 infection and for those with HPV58 A1 variant infection., Conclusions: These findings suggest that for a given HPV type, intratypic nucleotide changes may alter phenotypic traits that affect the probability of neoplasia., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Our objective was to compare human papillomavirus (HPV) detection in paired self-collected vaginal samples transported by overnight mail in liquid specimen transport medium (STM) (wet) or in dry tubes (dry). Women aged 18-24 years were recruited online to self-collect vaginal swab samples at home for HPV testing and 159 women returned paired wet and dry samples. Dry samples were rehydrated with STM upon arrival at the laboratory. HPV was detected by the Roche Linear Array HPV genotyping test (37 genotypes) and Kappa and McNemar statistics were used to compare wet versus dry samples for detecting HPV. Of the subjects tested in this study, 51 % were HPV-positive (in either sample) and 40 % were positive for high-risk HPV. A total of 216 type-specific infections were detected among the 80 HPV-positive women. Almost perfect agreement was observed between paired samples for detecting any HPV (subject-level positive agreement: 91.9 %, κ: 0.85) or type-specific HPV (positive agreement across types: 90.1 %, κ: 0.90). Similar agreement between sample types was seen when testing for high-risk types and 81.9 % of all type-specific infections were detected in both samples. Among discordant pairs, wet samples were 3.3 times more likely to be positive for type-specific HPV than dry samples (P = 0.02). However, in 63.6 % of wet-positive/dry-negative discordant pairs analysed for viral load, type-specific HPV was either undetectable or detected at a low level (<100 copies) in the wet samples, suggesting that the majority of infections missed by using dry samples are less likely to be clinically relevant. Our results indicate that dry transport is a feasible option for transporting at-home self-collected vaginal samples for HPV DNA testing.

Background: In contrast to the wealth of data on human papillomavirus (HPV) infections in women, much less is known about HPV in men., Methods: Between June 2003 and March 2006, a total of 240 heterosexually active male university students 18-20 years of age were recruited for participation in a cohort study of HPV infection. Genital cell samples were collected, at 4-month intervals, for HPV-DNA analysis by polymerase chain reaction. The subjects maintained a Web-based journal of sexual activity., Results: At 24 months, the cumulative incidence of new infection of any genital HPV type was 62.4% (95% confidence interval [CI], 52.6%-72.2%). Acquisition rates did not differ by genital site (i.e., glans, penile shaft, or scrotum) of initial detection (P=.86). The most commonly detected types were HPV-84 and HPV-16. In multivariate analysis, a report of a new sex partner during the prior 0-4 (hazards ratio [HR], 2.0 [95% CI, 1.3-3.0]) and 5-8 (HR, 1.8 [95% CI, 1.2-2.7]) months and a history of smoking (HR, 1.6 [95% CI, 1.1-2.4]) were associated with an elevated risk of HPV acquisition., Conclusion: Genital HPV infection is common and multifocal in young men, and its incidence is higher than that reported for similar cohorts of young women. The high rates of HPV infection in men should be considered when strategies for the prevention of HPV infection in female adolescents and young women are being developed.