Strategies to Optimize Cervical Cancer Screening Rates Among Transgender and Gender-Diverse People Assigned Female at Birth.

Self-sampling for primary HPV detection for cervical cancer screening is now FDA-approved. Many persons interested in cervical cancer screening are eager to opt out of the invasive speculum exam and opt into the self-sampling. There is no limitation on which persons can choose self-sampling. Transgender, nonbinary, and gender-diverse assigned female at birth (TGD AFAB) people experience barriers such as gender dysphoria and discomfort with sensitive exams. They may find more comfort with this equivalent method of screening. However, no clinical guidelines describe the best practices to increase screening among this underserved population. Much community work needs to occur to make the language of screening gender-affirming for all participants. Solutions to currently invasive follow-up exams after abnormal screens need to be communicated in language directed by the TGD AFAB community.

Implementation of INHERET, an Online Family History and Cancer Risk Interpretation Program for Primary Care and Specialty Clinics.

BACKGROUND: Individuals at increased risk for cancer are ascertained at low rates of 1% to 12% in primary care (PC). Underserved populations experience disparities of ascertainment, but data are lacking. INHERET is an online personal and family history tool to facilitate the identification of individuals who are eligible, according to guidelines, to be counseled on germline genetic testing and risk management. PATIENTS AND METHODS: INHERET data entry uses cancer genetics clinic questionnaires and algorithms that process patient data through NCCN Clinical Practice Guidelines in Oncology and best practice guidelines. The tool was tested in silico on simulated and retrospective patients and prospectively in a pilot implementation trial. Patients in cancer genetics and in PC clinics were invited to participate via email or a card. Informed consent was completed online. RESULTS: INHERET aimed to integrate patient data by algorithms based on professional and best practice guidelines to elicit succinct, actionable recommendations that providers can use without affecting clinic workflow or encounter length. INHERET requires a 4th-grade reading level, has simple navigation, and produces data lists and pedigree graphs. Prospective implementation testing revealed understandability of 90% to 100%, ease of use of 85%, and completion rates of 85% to 100%. Physicians using INHERET reported no added time to their encounters when patients were identified for counseling. In a specialty genetics clinic, INHERET's data were input, on average, within 72 hours compared with 4 to 6 weeks through standard care, and the queue for scheduling patients decreased from 400 to fewer than 15 in <6 months. CONCLUSIONS: INHERET was found to be accessible for all education and age levels, except patients aged >70 years, who encountered more technical difficulties. INHERET aided providers in conveying high-risk status to patients and eliciting appropriate referrals, and, in a specialty clinic, it produced improved workflows and shortened queues.

Comparative predictors for cervical cancer screening in Southeast Michigan for Middle Eastern-North African (MENA), White and African American/black women.

The cervical cancer screening behaviors of Arab American women are not adequately understood, in part because Middle Eastern North African (MENA) descent is not a US Census category. Others have shown decreased cervical cancer screening in this race of women. Our primary aim is to evaluate the predictors of cervical cancer screening among MENA, White and Black women of southeast Michigan. A community-wide health survey reached MENA, White and Black populations asking self-report questions about health behaviors, attitudes, and medical history. Cervical cancer screening was considered up-to-date if it was reported to have occurred within the past three years. Survey responses were limited to women 30-65 years old and were analyzed with inferential and logistic regression models to determine risk factors for cervical cancer screening. Overall, 78% reported cervical cancer screening within the past three years. MENA women screened less often if time in the US was less than ten years (aOR 0.24 (0.05, 0.76)) compared to more than ten years and if single (aOR 0.27 (0.07, 0.97)) compared to married. Religion was not associated with screening in any study population. Those of all races without insurance screened significantly less often than those with insurance. The barriers to cervical cancer screening among MENA women are not associated with religion but instead with lack of insurance and length of time residing in the US.

Patient-centered home cancer screening attitudes during SARS-CoV-2 pandemic.

COVID-19 has caused disruptions in health care, in particular cancer screenings. The primary aim of our work was to evaluate the degree to which populations were accepting of home-based screenings for colorectal cancer (CRC) and cervical cancer (primary HPV testing). Three groups of adults having distinct health burdens which may affect acceptance of home-based cancer screening were identified through outpatient electronic medical records as follows as either having survived a COVID hospitalization, having been positive for non-COVID respiratory illness or having type 2 diabetes. 132 respondents (58% female) completed an online survey with hypothetical cases about their acceptance of home-based CRC or cervical cancer screening. Among females, urine and vaginal screening for primary HPV testing was acceptable to 64% and 59%, respectively. Among both males and females, CRC home screening with fecal immunochemical test (FIT) or Cologuard was acceptable to 60% of the respondents. When adjusting for education, women with a positive attitude toward home-based urine /vaginal screening were 49 times and 23 times more likely to have a positive attitude toward CRC screening (aOR=48.7 (95% CI: 7.1, 337) and aOR=23.2 (95% CI: 3.8, 142), respectively). This report indicates that home-based cancer screens for CRC and primary HPV testing are acceptable to men and women and may allow for greater compliance with screening in the future.

The future of cancer screening after COVID-19 may be at home.

LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic, cancer screening decreased precipitously; home screening for colorectal cancer diminished less than that for colonoscopy and breast and cervical cancer screening. The authors have highlighted approaches for home cancer screening in addition to telemedicine.

Predictors of Human Papillomavirus Seropositivity in Appalachian Women Aged 18 to 26 Years.

BACKGROUND: Key informants of the Appalachian community questioned whether their unique environmental stressors would alter their immune response to human papillomavirus (HPV) infections. The primary aim of this study is to determine predictors of HPV seroprevalence to at least 1 of the 4 vaccine-related HPV types before vaccination using a psychoneuroimmunologic model in Appalachian women. METHOD: Women aged 18 to 26 years (n = 185) who had not received HPV vaccination provided cervical HPV DNA and blood samples. Human papillomavirus DNA was identified through Hybrid Capture 2 assay and then genotyped for HPV types 6, 11, 16, and 18 by Roche Linear Array. Competitive Luminex Immunoassay measured the type-specific antibodies to HPV types 6, 11, 16, and 18 in milli-Merck units per milliliter. Nine psychoneuroimmunology scales measuring attributes of stress were self-completed. RESULTS: Human papillomavirus DNA was detected in 50% (92/183) of participants, with only 14% (26/183) positive for HPV-6/11/16/18 DNA. Seropositivity for at least one anti-HPV-6/11/16 or 18, on the other hand, was present in 35% (64/183) of women, with only 10% (19/183) concomitantly infected and seropositive for the vaccine-related types. The Perceived Stress Scale was not a strong predictor of HPV seropositivity. CONCLUSIONS: Both HPV infection and vaccine-related HPV type seropositivity is common among Appalachian women aged 18 to 26 years. The anticipated effect of environmental stressors on HPV seropositivity was not seen when multiple predictors were considered.

Annual Wellness Visits for Persons With Physical Disabilities Before and After ACA Implementation.

PURPOSE: Persons with disabilities often experience uncoordinated health care, with repeated out-of-pocket copays. One purpose of the Patient Protection and Affordable Care Act (ACA) was to create zero copays for preventive health care including an annual wellness visit (AWV). The purpose of this study was to document the use of AWVs by persons with physical disabilities during the ACA rollout. METHODS: An administrative claims database, including both Medicare Advantage (MA) and commercial (COM) payers from 2008 to 2016, was used to identify unique wellness visits for adults with physical disabilities. We used interrupted time series analysis to compare AWV use by insurance type, sex, disability type, and race over time. RESULTS: The proportion of zero copays provided a timeline of ACA implementation categorized as pre-ACA, ACA-implementation, and post-ACA periods. By 2016, AWV use maximized at 47.6% (95% CI, 44.7%-50.8%) among COM-insured White women with congenital disabilities. By 2016, the lowest AWV use reached one-half the maximum, at 21.6% (95% CI, 18.4%-25.2%) among COM-insured Hispanic men with acquired disabilities. MA-insured Black and Hispanic men with acquired disabilities reached similarly low levels of AWV use. CONCLUSION: The ACA mandated zero copays, thereby allowing persons with physical disabilities the option for preventive health care without cost. Insurance type and sex significantly influenced AWV use, followed by disability type and race. Gaps in AWV use were exposed by insurance type, sex, disability, and race for persons with disabilities. Gaps in AWV use were also exposed between the general population and persons with disabilities.Annals "Online First" article.

Three large scale surveys highlight the complexity of cervical cancer under-screening among women 45-65years of age in the United States.

BACKGROUND: Large scale United States (US) surveys guide efforts to maximize the health of its population. Cervical cancer screening is an effective preventive measure with a consistent question format among surveys. The aim of this study is to describe the predictors of cervical cancer screening in older women as reported by three national surveys. METHODS: The Behavioral Risk Factor Surveillance System (BRFSS 2016), the Health Information National Trends Survey (HINTS 2017), and the Health Center Patient Survey (HCPS 2014) were analyzed with univariate and multivariate analyses. We defined the cohort as women, without hysterectomy, who were 45-65years old. The primary outcome was cytology within the last 3years. RESULTS: Overall, Pap screening rates were 71% (BRFSS), 79% (HINTS) and 66% (HCPS), among 41,657, 740 and 1571 women, respectively. BRFSS showed that women 60-64years old (aPR=0.88, 95% CI: 0.85, 0.91), and in rural locations (aPR=0.95, 95% CI: 0.92, 0.98) were significantly less likely to report cervical cancer screening than women 45-49-years old or in urban locations. Compared to less than high school, women with more education reported more screening (aPR=1.20, 95% CI: 1.13, 1.28), and those with insurance had higher screening rates than the uninsured (aPR=1.47, 95% CI: 1.33, 1.62). HINTS and HCPS also showed these trends. CONCLUSIONS: All three surveys show that cervical cancer screening rates in women 45-65years are insufficient to reduce cervical cancer incidence. Insurance is the major positive predictor of screening, followed by younger age and more education. Race/ethnicity are variable predictors depending on the survey.

Determinants of Acquisition and Clearance of Human Papillomavirus Infection in Previously Unexposed Young Women.

BACKGROUND: Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV. METHODS: Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000-September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time. RESULTS: On short-term follow-up (0-27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64-34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37-3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19-3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0-76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08-1.78) and black women (RR, 1.64; 95% CI, 1.04-2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43-0.98). CONCLUSIONS: We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.

The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up.

BACKGROUND: While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types. METHODS: Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug. RESULTS: Of the 129 women randomized to vaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24% vs. 10%, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21% vs. 0%, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions. CONCLUSIONS: The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.

HPV vaccines - A review of the first decade.

Pre-adolescent girls (9-15years) have the option of receiving a two dose HPV vaccine series at either a six month or one year interval to provide protection from HPV 16, the most prevalent type associated with cervical cancers, as well as several other less prevalent types. This series of vaccinations is highly likely to protect her from HPV infection until she enters the routine screening program, whether that be primary HPV testing or a combination of HPV testing and cytology. The two dose program has been recommended by the World Health Organization (WHO) since 2015. For women 15years and older, the three dose vaccine schedule is still recommended. The past ten years of Gardasil use has provided evidence of reduced HPV 16/18 infections in countries where there has been high coverage. Gardasil9 has replaced Gardasil. Gardasil9 has the same rapid anti-HPV 18 and HPV45 titer loss as Gardasil did. Cervarix remains equivalent to Gardasil9 in the prevention of HPV infections and precancers of any HPV type; Cervarix also has demonstrated sustained high antibody titers for at least 10years. One dose of Cervarix provides protection against HPV 16/18 infection with robust antibody titers well above natural infection titers. This may offer the easiest and most cost effective vaccination program over time, especially in low and lower middle income countries. Cervical cancer screening must continue to control cancer incidence over the upcoming decades. Future studies of prophylactic HPV vaccines, as defined by the WHO, must demonstrate protection against six month type specific persistent infections, not actual cervical cancer precursor disease endpoints, such as cervical intraepithelial neoplasia grade 3 (CIN 3) or adenocarcinoma in situ (AIS). This simplifies and makes less expensive future comparative studies between existing and new generic vaccines.

Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study.

The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p < 0.0001]). The next highest risk was with HPV-16 (21.1 [6.3-70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV-18, HPV-31, and HPV-45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15-25 years in PATRICIA.