Methylation markers for anal cancer screening: A repeated cross-sectional analysis of people living with HIV, 2015-2016.

People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high-grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low-grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high-resolution anoscopy (HRA) in Seattle, Washington, 2015-2016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0 years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01-1.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08-1.20) methylation were significantly associated with HSIL versus NILM/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01-1.11) and FMN2 (aOR: 1.13, 95% CI: 1.08-1.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.

Determinants of Type-Specific Human Papillomavirus Concordance Across Anatomic Sites in Young Men Who Have Sex With Men and Transgender Women, 3 U.S. Cities, 2016-2018.

BACKGROUND: Among men who have sex with men (MSM) and transgender women (TGW), the dynamics of human papillomavirus (HPV) infections at different anatomical sites are not well understood. Information on HPV concordance between anatomic sites can inform the extent of autoinoculation, and susceptibility of different anatomic areas to HPV infection. We described and assessed correlates of HPV concordance across anal, oral, and genital samples. METHODS: We enrolled 1876 MSM and TGW aged 18 to 26 years in 3 US cities. Oral, genital, and anal samples were self-collected for type-specific HPV DNA testing (37 types). Demographics, sexual behaviors, and health history were self-reported. Kappa statistics based on percent positive agreement (kappa+) and generalized estimating equations were used to describe and identify correlates of HPV type-specific concordance between anatomic sample pairs. RESULTS: Any HPV was detected in 69.9%, 48.6%, and 7.4% of anal, genital, and oral samples, respectively. Detection of any HPV (concurrence) was most common in anal-genital pairs (40.9%) and uncommon in oral-genital and oral-anal pairs (3.4% and 6.5% respectively). Type-specific concordance was poor across all sample pairs (kappa+ <0.20). Younger age and older age at first sex were positively associated with type-concordant anal-genital infections. Sexual behaviors were unassociated with concordance. CONCLUSIONS: Poor oral/anogenital concordance suggests the oral mucosa has different susceptibility to HPV infection, differential clearance and/or autoinoculation between oral and anogenital sites is unlikely. There was some observed concurrence and concordance between anal and genital sites, unassociated with sexual behavior, suggesting autoinoculation. Longitudinal studies are necessary to further elucidate mechanisms of multisite infections.

Association of Maternal Cervical Cancer Screening Adherence with Adolescent HPV Vaccination Among Adolescent-Mother Pairs.

Less than two-thirds of US adolescents are up-to-date with HPV vaccination. While mothers engaged in preventive care are more likely to seek preventive care for their children, current studies on associations between maternal cervical cancer screening (CCS) and adolescent HPV vaccination are needed. We assessed associations between maternal preventive service utilization and adolescent HPV vaccination using electronic health record data from a healthcare system in Washington State. We included adolescents (11-17 years) and their mothers with ≥ 1 primary care visit between 2018 and 2020. Outcomes were HPV vaccine initiation and completion. The primary exposure was maternal adherence to guideline-recommended CCS. Secondary exposures were maternal breast cancer screening adherence (for mothers ≥ 52 years) and ≥ 1 wellness visit ≤ 2 years. We used Generalized Estimating Equations to estimate prevalence ratios, and explore effect modification by adolescent sex, adolescent provider characteristics, and maternal language interpreter use. Of 4121 adolescents, 66% had a CCS-adherent mother, 82% initiated HPV vaccination, and 49% completed the series. CCS adherence was associated with higher initiation (adjusted prevalence ratio (APR):1.10, 95%CI:1.06-1.13) and completion (APR:1.16, 95%CI:1.08-1.23). Associations were stronger for male vs. female adolescents, adolescents who had a primary care provider in family practice vs. pediatrics, and adolescents who had the same primary care provider as their mother vs. not. Recent maternal wellness visit was also associated with higher initiation (APR:1.04, 95%CI:1.01-1.07) and completion (APR:1.12, 95%CI:1.05-1.20). Results suggest that delivering healthcare through a family-centered approach and engaging mothers in broad preventive care could increase adolescent HPV vaccination coverage.

Effect of Human Immunodeficiency Virus Infection on Human Papillomavirus Clearance Among Women in Senegal, West Africa.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is associated with development of invasive cervical cancer. METHODS: Longitudinal data was collected from 174 Senegalese women. We employed marginal Cox proportional hazards models to examine the effect of human immunodeficiency virus (HIV) status (HIV positive vs HIV negative) and HIV type (HIV-1 vs HIV-2 vs dual HIV-1/HIV-2) on clearance of type-specific HPV infection. Analyses were stratified by incident versus prevalent HPV infection. RESULTS: Incident HPV infections in HIV-positive women were less likely to clear than those in HIV-negative women (adjusted hazard ratio [HR] = 0.60; 95% confidence interval [CI], .38-.94). Among HIV-positive women, HIV-2-infected women and HIV-1/2 dually infected women were more likely to clear HPV incident infections than HIV-1-infected women (HR = 1.66; 95% CI, .95-2.92 and HR = 2.17; 95% CI, 1.12-4.22, respectively). Incident HPV infections in HIV-positive women with CD4 cell count ≤500 cells/µL were less likely to clear than those in HIV-positive women with CD4 cell count >500 cells/µL (HR = 0.65; 95% CI, .42-1.01). No significant associations were observed for prevalent HPV infections. CONCLUSIONS: HIV infection reduced the likelihood of clearance of incident HPV infection. Furthermore, among HIV-positive women, low CD4 cell count and dual HIV infection were each associated with reduced likelihood of clearance.

Implementation studio: implementation support program to build the capacity of rural community health educators serving immigrant communities to implement evidence-based cancer prevention and control interventions.

PURPOSE: Rural community-based organizations (CBOs) serving immigrant communities are critical settings for implementing evidence-based interventions (EBIs). The Implementation Studio is a training and consultation program focused on facilitating the selection, adaptation, and implementation of cancer prevention and control EBIs. This paper describes implementation and evaluation of the Implementation Studio on CBO's capacity to implement EBIs and their clients' knowledge of colorectal cancer (CRC) screening and intention to screen. METHODS: Thirteen community health educators (CHEs) from two CBOs participated in the Implementation Studio. Both CBOs selected CRC EBIs during the Studio. The evaluation included two steps. The first step assessed the CHEs' capacity to select, adapt, and implement an EBI. The second step assessed the effect of the CHEs-delivered EBIs on clients' knowledge of CRC and intention to screen (n = 44). RESULTS: All CHEs were Hispanic and women. Pre/post-evaluation of the Studio showed an increase on CHEs knowledge about EBIs (pre: 23% to post: 75%; p < 0.001). CHEs' ability to select, adapt, and implement EBIs also increased, respectively: select EBI (pre: 21% to post: 92%; p < 0.001), adapt EBI (pre: 21% to post: 92%; p < 0.001), and implement EBI (pre: 29% to post: 75%; p = 0.003). Pre/post-evaluation of the CHE-delivered EBI showed an increase on CRC screening knowledge (p < 0.5) and intention to screen for CRC by their clients. CONCLUSION: Implementation Studio can address unique needs of low resource rural CBOs. An implementation support program with training and consultation has potential to build the capacity of rural CBOs serving immigrant communities to implementation of cancer prevention and control EBIs. CLINICAL TRIALS REGISTRATION NUMBER: NCT04208724 registered.

The Association Between Adverse Childhood Experiences and Human Papillomavirus Vaccination Coverage in US Young Adults: A Cross-Sectional Study.

BACKGROUND: Adverse childhood experiences (ACEs) contribute to adverse health outcomes in adulthood. Access to preventive health care services, including genital human papillomavirus (HPV) vaccinations, may mitigate the impact of ACEs on adverse health outcomes. Our objective was to assess associations between ACEs and HPV vaccination coverage among young adults. METHODS: We included 3415 respondents aged 18 to 29 years to the 2019-2020 Behavioral Risk Factor Surveillance System ACE and HPV vaccination modules. Adverse childhood experiences included emotional, physical, and sexual abuse; household intimate partner violence, substance abuse, and mental illness; and parental separation/divorce and incarcerated household member. We used log-binomial regression models to calculate prevalence ratios (PRs) with 95% confidence intervals (CI) for associations between ACEs and self-reported HPV vaccination and completion. Secondary outcomes included influenza vaccination uptake, time since routine checkup, HIV testing history, and HIV-related risk behavior. RESULTS: Several ACEs were positively associated with HPV vaccination initiation, including emotional abuse (PR, 1.29; 95% CI, 1.17-1.43), intimate partner violence (PR, 1.14; 95% CI, 1.00-1.30), substance abuse (PR, 1.20; 95% CI, 1.08-1.33), and mental illness (PR, 1.35; 95% CI, 1.22-1.50). Similar associations were observed for completion. Conversely, most ACEs were negatively associated with influenza vaccination (PRs from 0.72 to 1.00) and with recent checkup (PRs from 0.92 to 1.00). Adverse childhood experiences were positively associated with having had an HIV test (PRs from 1.19 to 1.56) and HIV-related risk behavior (PRs from 1.19 to 2.07). CONCLUSIONS: The unexpected positive associations between ACEs and HPV vaccination coverage could be due to opportunities to receive HPV vaccination in late adolescence or early adulthood while accessing STI/HIV prevention or treatment services. Future studies should evaluate associations between ACEs and timely HPV vaccination in early adolescence.

Evaluation of Harms Reporting in U.S. Cancer Screening Guidelines.

BACKGROUND: Cancer screening should be recommended only when the balance between benefits and harms is favorable. This review evaluated how U.S. cancer screening guidelines reported harms, within and across organ-specific processes to screen for cancer. OBJECTIVE: To describe current reporting practices and identify opportunities for improvement. DESIGN: Review of guidelines. SETTING: United States. PATIENTS: Patients eligible for screening for breast, cervical, colorectal, lung, or prostate cancer according to U.S. guidelines. MEASUREMENTS: Information was abstracted on reporting of patient-level harms associated with screening, diagnostic follow-up, and treatment. The authors classified harms reporting as not mentioned, conceptual, qualitative, or quantitative and noted whether literature was cited when harms were described. Frequency of harms reporting was summarized by organ type. RESULTS: Harms reporting was inconsistent across organ types and at each step of the cancer screening process. Guidelines did not report all harms for any specific organ type or for any category of harm across organ types. The most complete harms reporting was for prostate cancer screening guidelines and the least complete for colorectal cancer screening guidelines. Conceptualization of harms and use of quantitative evidence also differed by organ type. LIMITATIONS: This review considers only patient-level harms. The authors did not verify accuracy of harms information presented in the guidelines. CONCLUSION: The review identified opportunities for improving conceptualization, assessment, and reporting of screening process-related harms in guidelines. Future work should consider nuances associated with each organ-specific process to screen for cancer, including which harms are most salient and where evidence gaps exist, and explicitly explore how to optimally weigh available evidence in determining net screening benefit. Improved harms reporting could aid informed decision making, ultimately improving cancer screening delivery. PRIMARY FUNDING SOURCE: National Cancer Institute.

Provider- and Facility-Level Variation in Precancerous Cervical Biopsy Diagnoses.

OBJECTIVES: Reproducibility of cervical biopsy diagnoses is low and may vary based on where the diagnostic test is performed and by whom. Our objective was to measure multilevel variation in diagnoses across colposcopists, pathologists, and laboratory facilities. METHODS: We cross-sectionally examined variation in cervical biopsy diagnoses within the 5 sites of the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR I) consortium within levels defined by colposcopists, pathologists, and laboratory facilities. Patients aged 18 to 65 years with a colposcopy with biopsy performed were included, with diagnoses categorized as normal, cervical intraepithelial neoplasia grade 1 (CIN1), grade 2 (CIN2), and grade 3 (CIN3). Using Markov Chain Monte-Carlo methods, we fit mixed-effects logistic regression models for biopsy diagnoses and presented median odds ratios (MORs), which reflect the variability within each level. Median odds ratios can be interpreted as the average increased odds a patient would have for a given outcome (e.g., CIN2 or CIN3 vs normal or CIN1) when switching to a provider with higher odds of diagnosing that outcome. The MOR is always 1 or greater, and a value of 1 indicates no variation in outcome for that level, with higher values indicating greater variation. RESULTS: A total of 130,110 patients were included who received care across 82 laboratory facilities, 2,620 colposcopists, and 489 pathologists. Substantial variation in biopsy diagnoses was found at each level, with the most occurring between laboratory facilities, followed by pathologists and colposcopists. Substantial variation in biopsy diagnoses of CIN2 or CIN3 (vs normal or CIN1) was present between laboratory facilities (MOR: 1.26; 95% credible interval = 1.19-1.36). CONCLUSIONS: Improving consistency in cervical biopsy diagnoses is needed to reduce underdiagnosis, overdiagnosis, and unnecessary treatment resulting from variation in cervical biopsy diagnoses.

Strategies to Increase Cervical Cancer Screening With Mailed Human Papillomavirus Self-Sampling Kits: A Randomized Clinical Trial.

Importance: Optimal strategies for increasing cervical cancer screening may differ by patient screening history and health care setting. Mailing human papillomavirus (HPV) self-sampling kits to individuals who are overdue for screening increases adherence; however, offering self-sampling kits to screening-adherent individuals has not been evaluated in the US. Objective: To evaluate the effectiveness of direct-mail and opt-in approaches for offering HPV self-sampling kits to individuals by cervical cancer screening history (screening-adherent and currently due, overdue, or unknown). Design, Setting, and Participants: Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Individuals aged 30 to 64 years with female sex, a primary care clinician, and no hysterectomy were identified through electronic health records (EHRs) and enrolled between November 20, 2020, and January 28, 2022, with follow-up through July 29, 2022. Interventions: Individuals stratified as due (eg, at the time of randomization, these individuals have been previously screened and are due for their next screening in ≤3 months) were randomized to receive usual care (patient reminders and clinician EHR alerts [n = 3671]), education (usual care plus educational materials about screening [n = 3960]), direct mail (usual care plus educational materials and a mailed self-sampling kit [n = 1482]), or to opt in (usual care plus educational materials and the option to request a kit [n = 3956]). Individuals who were overdue for screening were randomized to receive usual care (n = 5488), education (n = 1408), or direct mail (n = 1415). Individuals with unknown history for screening were randomized to receive usual care (n = 2983), education (n = 3486), or to opt in (n = 3506). Main Outcomes and Measures: The primary outcome was screening completion within 6 months. Primary analyses compared direct-mail or opt-in participants with individuals randomized to the education group. Results: The intention-to-treat analyses included 31 355 randomized individuals (mean [SD] age, 45.9 [10.4] years). Among those who were due for screening, compared with receiving education alone (1885 [47.6%]), screening completion was 14.1% (95% CI, 11.2%-16.9%) higher in the direct-mail group (914 [61.7%]) and 3.5% (95% CI, 1.2%-5.7%) higher in the opt-in group (2020 [51.1%]). Among individuals who were overdue, screening completion was 16.9% (95% CI, 13.8%-20.0%) higher in the direct-mail group (505 [35.7%]) compared with education alone (264 [18.8%]). Among those with unknown history, screening was 2.2% (95% CI, 0.5%-3.9%) higher in the opt-in group (634 [18.1%]) compared with education alone (555 [15.9%]). Conclusions and Relevance: Within a US health care system, direct-mail self-sampling increased cervical cancer screening by more than 14% in individuals who were due or overdue for cervical cancer screening. The opt-in approach minimally increased screening. To increase screening adherence, systems implementing HPV self-sampling should prioritize direct-mail outreach for individuals who are due or overdue for screening. For individuals with unknown screening history, testing alternative outreach approaches and additional efforts to document screening history are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04679675.

Effectiveness of Human Papillomavirus (HPV) Vaccination Against Penile HPV Infection in Men Who Have Sex With Men and Transgender Women.

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.

Sensitivity of Self-Reported Human Papillomavirus Vaccination History Among 18- to 26-Year-Old Men Who Have Sex With Men: Seattle, WA, 2016 to 2018.

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.

Does mailing unsolicited HPV self-sampling kits to women overdue for cervical cancer screening impact uptake of other preventive health services in a United States integrated delivery system?

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.

Understanding the Role of Emerging Vitamin D Biomarkers on Short-term Persistence of High-Risk Human Papillomavirus Infection Among Mid-Adult Women.

BACKGROUND: Associations between vitamin D biomarkers and persistent high-risk human papillomavirus (hrHPV) detection have not been evaluated. METHODS: 2011-2012 stored sera from 72 women aged 30-50 years with prevalent hrHPV (n = 116 type-specific infections) were tested for 5 vitamin D biomarkers: 25(OH)D and 4 emerging biomarkers, 1,25(OH)2D; 24,25(OH)2D; free vitamin D; and vitamin D binding protein (DBP). The hrHPV detection patterns (persistent vs transient/sporadic) were determined using cervicovaginal swabs collected monthly for 6 months. Associations between vitamin D and short-term type-specific hrHPV persistence were estimated using logistic regression. Our primary exposure was continuous 25(OH)D, with additional biomarkers evaluated as secondary exposures. Primary models were adjusted for age, race, body mass index, education, contraceptives, smoking, season, and calcium/phosphate levels. Sensitivity analyses were restricted from 19 hrHPV types to 14 used in cervical cancer screening. RESULTS: In primary analyses, nonsignificant positive associations with hrHPV persistence were observed for measures of 25(OH)D and 24,25(OH)2D. Associations were stronger and significant when restricting to 14 hrHPV types (25(OH)D per 10 ng/mL increase: adjusted odds ratio [aOR], 1.82 [95% confidence interval {CI}, 1.15-2.88] and aOR, 4.19 [95% CI, 1.18-14.88] DBP-adjusted; 25(OH)D ≥30 vs <30 ng/mL: aOR, 8.85 [95% CI, 2.69-29.06]; 24,25(OH)2D: aOR, 1.85 [95% CI, 1.18-2.88]). 1,25(OH)2D was unassociated with persistence. CONCLUSIONS: Serum vitamin D measured by multiple biomarkers showed positive associations with short-term hrHPV persistence that were significant only when restricting to 14 clinically relevant hrHPV types.

Detection of 14 High-Risk Human Papillomaviruses Using Digital LAMP Assays on a Self-Digitization Chip.

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.

Out of reach? Correlates of cervical cancer underscreening in women with varying levels of healthcare interactions in a United States integrated delivery system.

One in five U.S. women with health insurance are underscreened for cervical cancer. We sought to identify whether underscreening correlates differed among women with different levels of health care interaction. Among women age 30-64 years who were members of an integrated U.S. health system, we used 2014-2015 electronic health record data to identify underscreened cases (≥3.4 years since last Papanicolaou (Pap) test, n=3352) and screening-adherent controls (<3.4 years since last Pap test, n=45,359) and extracted data on potential underscreening correlates (demographics, health history, and healthcare utilization). We calculated the odds of underscreening in the total population and by subgroups defined by healthcare visits and online health portal usage in the prior 12 months. Underscreening was associated with older age (50-64 vs. 30-39; odds ratio (OR)=1.6; 95%CI=1.4-1.8), current tobacco use (vs. never use; OR=2.1; 95%CI=1.8-2.2), higher BMI (≥35 kg/m2 vs <25 kg/m2, OR=2.0; 95%CI=1.8-2.3), screening non-adherence for colorectal cancer (OR=5.1; 95%CI=4.6-5.7) and breast cancer (OR=8.1, 95%CI=7.2-9.0), and having no recent visit with their primary care provider (PCP) nor recent health portal use (vs. recent PCP visit and portal use; OR=8.4, 95%CI=7.6-9.4). Underscreening correlates were similar between the total study population and within all healthcare interaction groups. Interaction with the healthcare system is associated with lower odds of underscreening, but sociodemographic and health status correlates are similar regardless of primary care visits or online portal use. These data support the need for additional interventions to reach insured women who remain underscreened for cervical cancer.

Achieving cervical cancer elimination among Indigenous women.

Achieving the World Health Organisation (WHO) cervical cancer elimination target of fewer than four new cases per 100,000 woman-years requires scaling up HPV vaccination of girls, cervical screening, and pre-cancer and cancer treatment. We reviewed data from four high-income colonised countries (Australia, Canada, Aotearoa New Zealand (NZ), and the United States (US)) to identify how each is currently performing compared to the cervical cancer incidence elimination and triple-intervention targets, nationally and in Indigenous women. We also summarise barriers and enablers to meeting targets for Indigenous women. To achieve elimination, cervical cancer incidence must be reduced by 74% in Indigenous women in Australia, and 63% in Maori women in NZ; data were not published in sufficient detail to compare incidence in Indigenous women in Canada or the US to the WHO target. Only Australia meets the vaccination coverage target, but uptake appears comparatively equitable within Australia, NZ and the US, whereas there appears to be a substantial gap in Canada. Screening coverage is lower for Indigenous women in all four countries though the differential varies by country. Currently, only Australia universally offers HPV-based screening. Data on pre-cancer and cancer treatment were limited in all countries. Large inequities in cervical cancer currently exist for Indigenous peoples in Australia, Canada, New Zealand and the US, and elimination is not on track for all women in these countries. Current data gaps hinder improvements. These countries must urgently address their systemic failure to care and provide health care for Indigenous women.

Development of a theory-based HPV vaccine promotion comic book for East African adolescents in the US.

BACKGROUND: Human Papillomavirus (HPV) vaccine uptake is low among East African adolescents in the US. Adolescents' preferences influence HPV vaccine decisions, yet few interventions exist that address East African adolescents' beliefs about HPV vaccines. We describe a multi-step process on how to create a theory-based comic book by integrating empirical findings, theory and focus group data from East African parents in the US. METHODS: Our multi-methods process included conducting focus groups with Somali, Ethiopian, and Eritrean mothers (n = 30) to understand mothers and adolescents socio-cultural beliefs and information needs about the HPV vaccine, creating comic book messages integrating the focus group findings, and assessing the acceptability of the finalized comic book among Somali, Ethiopian, and Eritrean adolescents (n = 134). RESULTS: We identified categories around socio-cultural beliefs (such ethnic representation and concerns about pork gelatin in vaccines), HPV vaccine information needs, and diffusion of information. We then mapped the categories to theoretical constructs and operationalized them into the comic book. Finally, we describe the overall acceptability of the comic book and specifics on comic book structure, appeal of characters, and message relevance. CONCLUSIONS: A rigorous multi-step process that integrates theory and focus group data can help create culturally appropriate health messages that can educate and appeal to the community.

Vaccine Effectiveness Against Prevalent Anal and Oral Human Papillomavirus Infection Among Men Who Have Sex With Men-United States, 2016-2018.

BACKGROUND: In the United States, human papillomavirus (HPV) vaccination has been recommended for young adult men who have sex with men (MSM) since 2011. METHODS: The Vaccine Impact in Men study surveyed MSM and transgender women aged 18-26 years in 3 US cities during 2016-2018. Self-collected anal swab and oral rinse specimens were assessed for 37 types of HPV. We compared HPV prevalence among vaccinated and unvaccinated participants and determined adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). RESULTS: Among 1767 participants, 704 (39.8%) self-reported receiving HPV vaccine. Median age at vaccination (18.7 years) was older than age at first sex (15.7 years). Quadrivalent vaccine-type HPV was detected in anal or oral specimens from 475 (26.9%) participants. Vaccine-type HPV prevalence was lower among vaccinated (22.9%) compared with unvaccinated (31.6%) participants; aPR for those who initiated vaccination at age ≤18 years was 0.41 (CI, 0.24-0.57) and at age >18 years was 0.82 (CI, 0.67-0.98). Vaccine effectiveness of at least 1 HPV vaccine dose at age ≤18 years or >18 years was 59% and 18%, respectively. CONCLUSIONS: Findings suggest real-world effectiveness of HPV vaccination among young adult MSM. This effect was stronger with younger age at vaccination.

Impact of Caregiving During Emerging Adulthood on Frequent Mental Distress, Smoking, and Drinking Behaviors: United States, 2015-2017.

Objectives. To examine associations between caregiving mental or behavioral health outcomes among emerging US adults, defined as persons aged 18 to 25 years.Methods. The study sample included emerging adult respondents to the 2015-2017 Behavioral Risk Factor Surveillance System's caregiving module. Exposures were caregiver (n = 3087), expectant caregiver (n = 2303), and noncaregiver (n = 12 216) status. Expectant caregivers were defined as persons not currently providing care but anticipating doing so within the next 2 years. Outcomes included frequent mental distress (FMD), drinking (binge or heavy), and current smoking (cigarette or e-cigarette use). We used robust Poisson regression to calculate adjusted prevalence ratios (APRs) and corresponding 95% confidence intervals (CIs). We adjusted all models for income.Results. Caregivers had a similar prevalence of FMD when compared with both expectant caregivers (APR = 1.67; 95% CI = 1.28, 2.17) and noncaregivers (APR = 1.50; 95% CI = 1.23, 1.82). Caregivers had a higher prevalence of current cigarette smoking compared with noncaregivers (APR = 1.44; 95% CI = 1.21, 1.71).Conclusions. Among emerging adults, providing care is associated with poorer mental health. Point estimates looking at FMD were higher when we compared caregivers with expectant caregivers, suggesting a difference in exchangeability between comparison groups.Public Health Implications. This study highlights the importance of including emerging adults in caregiving research.

Cost-effectiveness studies of HPV self-sampling: A systematic review.

HPV self-sampling (HPV-SS) can increase cervical cancer screening participation by addressing barriers in high- and low- and middle-income settings. Successful implementation of HPV-SS programs will depend on understanding potential costs and health effects. Our objectives were to summarize the methods and results of published HPV-SS cost and cost-effectiveness studies, present implications of these results for HPV-SS program implementation, and identify knowledge gaps. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. One reviewer searched online databases for articles published through June 12, 2019, identified eligible studies, and extracted data; a second reviewer checked extracted data for accuracy. Eligible studies used an economic model to compare HPV-SS outreach strategies to standard-of-care tests. Of 16 eligible studies, 14 reported HPV-SS could be a cost-effective strategy. Studies differed in model type, HPV-SS delivery methods, triage strategies for positive results, and target populations. Most (9/16) modeled HPV-SS in European screening programs, 6/16 targeted women who were underscreened for cervical cancer, and 5/16 modeled HPV-SS in low- and middle-income countries. The most commonly identified driver of HPV-SS cost-effectiveness was the level of increase in cervical cancer screening attendance. Lower HPV-SS material and testing costs, higher sensitivity to detect cervical precancer, and longer duration of underscreening among HPV-SS users were also associated with increased cost-effectiveness. Future HPV-SS models in high-income settings should explore the effect of widespread vaccination and new triage strategies such as partial HPV genotyping. Knowledge gaps remain about the cost-effectiveness of HPV-SS in low- and middle-income settings.