COVID-19 as a catalyst for reimagining cervical cancer prevention.

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally.

Factors associated with parental COVID-19 vaccine attitudes and intentions among a national sample of United States adults ages 18-45.

PURPOSE: This study explored factors associated with parents' attitudes and intentions to seek information about the COVID-19 vaccine for their children (ages 0-18) and intentions to vaccinate their age-eligible children. DESIGN AND METHODS: As part of an anonymous online cross-sectional survey, parents' vaccine attitudes, COVID-19 vaccine intentions for their children, health literacy, health numeracy, and sociodemographic variables were assessed. Multivariable ordered logistic regression models identified factors associated with parents' COVID-19 vaccine intentions for their children. RESULTS: Parents/guardians (n = 963) were mostly White (82.3%), insured (88.0%), and college graduates (57.3%). Men reported higher intentions than women to seek information about the COVID-19 vaccine for their children (p = 0.003) and higher intentions to vaccinate their children (p = 0.049). Parental characteristics associated with increased intentions to have their children vaccinated included higher educational attainment (p < 0.001), more positive general vaccine attitudes (p < 0.001), preference for health information in a language other than English (p = 0.006), higher income (p = 0.048), having health insurance (p = 0.05), health literacy (p = 0.024), and health numeracy (p = 0.049). CONCLUSIONS: Multiple sociodemographic characteristics including male gender, higher health literacy and numeracy, and language preference are noteworthy factors associated with parental COVID-19 vaccine intentions that could inform the planning and implementation of educational interventions. PRACTICE IMPLICATIONS: Nurses are important sources of trusted information and play an important role in parent/family health education and in understanding myriad factors that may improve attitudes and enhance readiness toward vaccine uptake. Our findings emphasize the potential value of examining tailored/targeted COVID-19 vaccine education according to key influencing factors.

Impact of the COVID-19 pandemic on human papillomavirus (HPV) vaccination among a national sample of United States adults ages 18-45: A cross-sectional study

To assess how the COVID-19 pandemic affected catch-up HPV vaccination among age-eligible adults (ages 18-45). The current study leverages a national, cross-sectional sample of US adults ages 18-45 years to assess the prevalence and determinants of COVID-19 pandemic-related disruptions to catch-up HPV vaccination in 2021. The sample was restricted to adults intending to receive the HPV vaccine. Multinomial logistic regression analysis was conducted to assess the probability of 1) pandemic-related HPV vaccination disruption and 2) uncertainty about pandemic-related HPV vaccination disruption. Report of ‘no pandemic-related HPV vaccination disruption’ served as the reference category. Among adults intending to get the HPV vaccine (n=1,683), 8.6% reported pandemic-related HPV vaccination disruption, 14.7% reported uncertainty about vaccination disruption, and 76.7% reported no disruption. Factors associated with higher odds of pandemic-related vaccination disruption included non-English language preference (OR: 3.20;95% CI: 1.99-5.13), being a parent/guardian (OR: 1.77;95% CI: 1.18-2.66), having at least one healthcare visit in the past year (OR: 1.97;95% CI: 1.10-3.53), being up-to-date on the tetanus vaccine (OR: 1.81;95% CI: 1.19-2.75), and being a cancer survivor (OR: 2.57;95% CI: 1.52-4.34). Catch-up HPV vaccination for age-eligible adults is a critical public health strategy for reducing HPV-related cancers. While a small percentage of adults reported pandemic-related disruptions to HPV vaccination, certain adults (e.g., individuals with a non-English language preference and cancer survivors) were more likely to report a disruption. Interventions may be needed that increase accessibility of catch-up HPV vaccination among populations with reduced healthcare access during the pandemic.

Long-Term CD4+ T-Cell and Immunoglobulin G Immune Responses in Oncology Workers following COVID-19 Vaccination: An Interim Analysis of a Prospective Cohort Study.

We conducted a prospective study to evaluate immune responses to SARS-CoV-2 in oncology workers in which we collected blood and clinical data every 6 months. Spike-specific CD4+ T-cells and immunoglobulin G responses were measured using interferon-gamma enzyme-linked immunosorbent spot and enzyme-linked immunosorbent assay, respectively. Sixty (81%) vaccinated and 14 (19%) unvaccinated individuals were enrolled. CD4+ T-cell responses of those individuals currently naturally infected were comparable to those who were 6 months from receiving their last dose of the vaccine; both responses were significantly higher than among those who were unvaccinated. Unvaccinated participants who became vaccinated while in the study showed a significant increase in both types of spike-specific immune responses. Previously vaccinated individuals who received a third dose (booster) showed a similar response to the spike protein. However, this response decreases as soon as 3 months but does not dip below the established response following two doses. Response to variants of concern B.1.617.2 (Delta) and B.1.1.529 (Omicron) also increased, with the Omicron variant having a significantly lower response when compared to Delta and the wild type. We conclude that antibody and T-cell responses increase in oncology workers after serial vaccination but can wane over time.

Strategies and Lessons Learned During Cleaning of Data From Research Panel Participants: Cross-sectional Web-Based Health Behavior Survey Study.

BACKGROUND: The use of web-based methods to collect population-based health behavior data has burgeoned over the past two decades. Researchers have used web-based platforms and research panels to study a myriad of topics. Data cleaning prior to statistical analysis of web-based survey data is an important step for data integrity. However, the data cleaning processes used by research teams are often not reported. OBJECTIVE: The objectives of this manuscript are to describe the use of a systematic approach to clean the data collected via a web-based platform from panelists and to share lessons learned with other research teams to promote high-quality data cleaning process improvements. METHODS: Data for this web-based survey study were collected from a research panel that is available for scientific and marketing research. Participants (N=4000) were panelists recruited either directly or through verified partners of the research panel, were aged 18 to 45 years, were living in the United States, had proficiency in the English language, and had access to the internet. Eligible participants completed a health behavior survey via Qualtrics. Informed by recommendations from the literature, our interdisciplinary research team developed and implemented a systematic and sequential plan to inform data cleaning processes. This included the following: (1) reviewing survey completion speed, (2) identifying consecutive responses, (3) identifying cases with contradictory responses, and (4) assessing the quality of open-ended responses. Implementation of these strategies is described in detail, and the Checklist for E-Survey Data Integrity is offered as a tool for other investigators. RESULTS: Data cleaning procedures resulted in the removal of 1278 out of 4000 (31.95%) response records, which failed one or more data quality checks. First, approximately one-sixth of records (n=648, 16.20%) were removed because respondents completed the survey unrealistically quickly (ie, <10 minutes). Next, 7.30% (n=292) of records were removed because they contained evidence of consecutive responses. A total of 4.68% (n=187) of records were subsequently removed due to instances of conflicting responses. Finally, a total of 3.78% (n=151) of records were removed due to poor-quality open-ended responses. Thus, after these data cleaning steps, the final sample contained 2722 responses, representing 68.05% of the original sample. CONCLUSIONS: Examining data integrity and promoting transparency of data cleaning reporting is imperative for web-based survey research. Ensuring a high quality of data both prior to and following data collection is important. Our systematic approach helped eliminate records flagged as being of questionable quality. Data cleaning and management procedures should be reported more frequently, and systematic approaches should be adopted as standards of good practice in this type of research.

Efficacy, immunogenicity, and safety of a quadrivalent HPV vaccine in men: results of an open-label, long-term extension of a randomised, placebo-controlled, phase 3 trial.

BACKGROUND: The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16-26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. METHODS: The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16-23 years) or men who have sex with men (MSM; aged 16-26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov, NCT00090285. FINDINGS: Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1-11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0-6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0-8·7) versus 137·3 (83·9-212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0-7·7) versus 140·4 (89·0-210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5-114·4) versus 906·2 (553·5-1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6-212·3] vs 0 cases per 10 000 person-years [0·0-13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0-215·7] vs 0 cases per 10 000 person-years [0·0-10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9-1289·1] vs 101·3 cases per 10 000 person-years [32·9-236·3]). No vaccine-related serious adverse events were reported. INTERPRETATION: The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. FUNDING: Merck Sharp & Dohme.

COVID-19 vaccine behaviors and intentions among a national sample of United States adults ages 18-45.

BACKGROUND: Vaccination for SARS-CoV-2, the virus that causes COVID-19 illness, is an important public health tool to reduce hospitalizations and deaths. PURPOSE: This report focuses on intentions and behaviors related to COVID-19 vaccination among United States (U.S.) adults ages 18-45. METHODS: From February 25-March 24, 2021, we conducted an online survey assessing COVID-19 vaccine intentions and behaviors, health beliefs, vaccine attitudes, and sociodemographic characteristics. Participants were adults aged 18-45, living throughout the U.S. with oversampling in Florida, panelists of a research panel company directly or via verified partners, and able to read, write, and understand English. Associations between COVID-19 vaccination uptake, intentions, and other study variables were examined through multivariable logistic and proportional odds regression analyses. RESULTS: Among participants in the final analytic sample (n = 2722), 18% reported having received at least one dose of a COVID-19 vaccine. Approximately 31% of unvaccinated participants reported strong intentions to receive a COVID-19 vaccine in the next year, whereas 35% reported strong intentions to receive a COVID-19 vaccine if it were strongly recommended by a healthcare provider. All COVID-19 vaccination outcomes were associated with male gender, sexual minority status, higher levels of education, and previous influenza vaccination. All vaccination intention outcomes were associated with vaccine attitudes and geographic region. Vaccination status and intentions were differentially associated with multiple additional sociodemographic, attitudinal, and/or healthcare experience variables. CONCLUSIONS: Several demographic variables, vaccine attitudes, and healthcare experiences were found to contribute to COVID-19 vaccine receipt and intentions. Targeted efforts are necessary to increase uptake of the vaccine in the U.S.

Evaluation of Antibody Response to SARS-CoV-2 mRNA-1273 Vaccination in Patients With Cancer in Florida.

Importance: Patients with cancer experience high rates of morbidity and mortality after SARS-CoV-2 infection. Immune response to mRNA-1273 vaccination across multiple cancer types and treatments remains to be established. Objective: To quantitate antibody responses after mRNA-1273 vaccination among patients with solid tumors and hematologic cancer and to assess clinical and treatment factors associated with vaccine response. Design, Setting, and Participants: This cohort study included patients with cancer who were aged 18 years or older, spoke English or Spanish, had received their first mRNA-1273 dose between January 12 and 25, 2021, and agreed to blood tests before and after vaccination. Exposures: Receipt of 1 and 2 mRNA-1273 SARS-CoV-2 vaccine doses. Main Outcomes and Measures: Seroconversion after each vaccine dose and IgG levels against SARS-CoV-2 spike protein obtained immediately before the first and second vaccine doses and 57 days (plus or minus 14 days) after the first vaccine dose. Cancer diagnoses and treatments were ascertained by medical record review. Serostatus was assessed via enzyme-linked immunosorbent assay. Paired t tests were applied to examine days 1, 29, and 57 SARS-CoV-2 antibody levels. Binding antibody IgG geometric mean titers were calculated based on log10-transformed values. Results: The 515 participants were a mean (SD) age of 64.5 (11.4) years; 262 (50.9%) were women; and 32 (6.2%) were Hispanic individuals and 479 (93.0%) White individuals; race and ethnicity data on 4 (0.7%) participants were missing. Seropositivity after vaccine dose 2 was 90.3% (465; 95% CI, 87.4%-92.7%) among patients with cancer, was significantly lower among patients with hematologic cancer (84.7% [255]; 95% CI, 80.1%-88.6%) vs solid tumors (98.1% [210]; 95% CI, 95.3%-99.5%), and was lowest among patients with lymphoid cancer (70.0% [77]; 95% CI, 60.5%-78.4%). Patients receiving a vaccination within 6 months after anti-CD20 monoclonal antibody treatment had a significantly lower seroconversion (6.3% [1]; 95% CI, 0.2%-30.2%) compared with those treated 6 to 24 months earlier (53.3% [8]; 95% CI, 26.6%-78.7%) or those who never received anti-CD20 treatment (94.2% [456]; 95% CI, 91.7%-96.1%). Low antibody levels after vaccination were observed among patients treated with anti-CD20 within 6 months before vaccination (GM, 15.5 AU/mL; 95% CI, 9.8-24.5 AU/mL), patients treated with small molecules (GM, 646.7 AU/mL; 95% CI, 441.9-946.5 AU/mL), and patients with low lymphocyte (GM, 547.4 AU/mL; 95% CI, 375.5-797.7 AU/mL) and IgG (GM, 494.7 AU/mL; 95% CI, 304.9-802.7 AU/mL) levels. Conclusions and Relevance: This cohort study found that the mRNA-1273 SARS-CoV-2 vaccine induced variable antibody responses that differed by cancer diagnosis and treatment received. These findings suggest that patients with hematologic cancer and those who are receiving immunosuppressive treatments may need additional vaccination doses.

Long-term impact of HPV vaccination and COVID-19 pandemic on oropharyngeal cancer incidence and burden among men in the USA: A modeling study.

BACKGROUND: Oropharyngeal cancer (OPC) incidence is rising rapidly among men in the United States of America (USA). We aimed to project the impact of maintaining the current HPV vaccination uptake and achieving 80% national (Healthy People) goal on OPC incidence and burden. METHODS: We developed an open-cohort micro-simulation model of OPC natural history among contemporary and future birth cohorts of men, accounting for sexual behaviors, population growth, aging, and herd immunity. We used data from nationally representative databases, cancer registries from all 50 states, large clinical trials, and literature. We evaluated the status quo scenario (the current HPV vaccination uptake remained stable) and alternative scenarios of improvements in uptake rates in adolescents (aged 9-17 years) and young adults (aged 18-26 years) by 2025 to achieve and maintain the 80% goal. The primary outcome was to project OPC incidence and burden from 2009 to 2100. We also assessed the impact of disruption in HPV vaccine uptake during the COVID-19 pandemic. FINDINGS: OPC incidence is projected to rise until the mid-2030s, reaching the age-standardized incidence rate of 9·8 (95% uncertainty interval [UI] 9·5-10·1) per 100 000 men, with the peak annual burden of 23 850 (UI, 23 200-24 500) cases. Under the status quo scenario, HPV vaccination could prevent 124 000 (UI, 117 000-131 000) by 2060, 400 000 (UI, 384 000-416 000) by 2080, and 792 000 (UI, 763 000-821 000) by 2100 OPC cases among men. Achievement and maintenance of 80% coverage among adolescent girls only, adolescent girls and boys, and adolescents plus young adults could prevent an additional number of 100 000 (UI, 95 000-105 000), 118 000 (UI, 113 000-123 000), and 142 000 (UI, 136 000-148 000) male OPC cases by 2100. Delayed recovery of the HPV vaccine uptake during the COVID-19 pandemic could lead to 600 (UI, 580-620) to 6200 (UI, 5940-6460) additional male OPC cases by 2100, conditional on the decline in the extent of the national HPV vaccination coverage and potential delay in rebounding. INTERPRETATION: Oropharyngeal cancer burden is projected to rise among men in the USA. Nationwide efforts to achieve the HPV vaccination goal of 80% coverage should be a public health priority. Rapid recovery of the declined HPV vaccination uptake during the COVID-19 pandemic is also crucial to prevent future excess OPC burden. FUNDING: National Cancer Institute and National Institute on Minority Health and Health Disparities of the USA.

Rationale and design of the Prevent Anal Cancer Self-Swab Study: a protocol for a randomised clinical trial of home-based self-collection of cells for anal cancer screening.

INTRODUCTION: Squamous cell carcinoma of the anus is a common cancer among sexual minority men, especially HIV-positive sexual minority men; however, there is no evidenced-based national screening protocol for detection of anal precancers. Our objective is to determine compliance with annual anal canal self-sampling or clinician-sampling for human papillomavirus (HPV) DNA. METHODS AND ANALYSIS: This is a prospective, randomised, two-arm clinical study to evaluate compliance with annual home-based versus clinic-based HPV DNA screening of anal canal exfoliated cells. The setting is primary care community-based clinics. Recruitment is ongoing for 400 HIV-positive and HIV-negative sexual minority men and transgender persons, aged >25 years, English or Spanish speaking, no current use of anticoagulants other than nonsteroidal anti-inflammatory drugs and no prior diagnosis of anal cancer. Participants are randomised to either receive a swab in the mail for home-based collection of an anal canal specimen at 0 and 12 months (arm 1) or attend a clinic for clinician collection of an anal canal specimen at 0 and 12 months (arm 2). Persons will receive clinic-based Digital Anal Rectal Examinations and high-resolution anoscopy-directed biopsy to assess precancerous lesions, stratified by study arm. Anal exfoliated cells collected in the study are assessed for high-risk HPV persistence and host/viral methylation. The primary analysis will use the intention-to-treat principle to compare the proportion of those who comply with 0-month and 12-month sampling in the home-based and clinic-based arms. The a priori hypothesis is that a majority of persons will comply with annual screening with increased compliance among persons in the home-based arm versus clinic-based arm. ETHICS AND DISSEMINATION: The study has been approved by the Medical College of Wisconsin Human Protections Committee. Results will be disseminated to communities where recruitment occurred and through peer-reviewed literature and conferences. TRIAL REGISTRATION NUMBER: NCT03489707.