Preventive Medicine

Human papillomavirus-associated cancers, precancers, and genital warts in Denmark, 2000–2022 – Current burden of disease and population impact of multi-cohort HPV vaccination

We present incidence trends of cancer and precancer at human papillomavirus(HPV)-associated sites, and genital warts, including the current burden of HPV-associated disease in Denmark, a country with multi-cohort HPV vaccination. Cases were identified from high-quality nationwide registries (2000-2022). The age-specific incidence rate, age-standardized incidence rate (ASR) and estimated annual percentage change (EAPC) were calculated according to sex and calendar year. The current burden (2020-2022) of HPV-associated disease was estimated as the average annual number of each lesion multiplied by the disease-specific HPV-attributable fraction. ASRs of cervical precancer and genital warts declined markedly in the post-HPV vaccination period - for genital warts corresponding to an EAPC of -13.7 % (-15.0;-12.4)(women) and -8.8 % (-9.4;-8.2)(men), respectively. ASRs of HPV-associated cancer sites increased continuously in men (EAPC: 2.8 % (2.2;3.5)), and the same was observed for non-cervical HPV-associated cancer sites in women (EAPC: 2.5 % (2.0;3.0)). Cervical cancer, however, decreased in the post-HPV vaccination period (EAPC: -2.7 % (-3.8;-1.5)). Age-specific incidence rates of HPV-associated cancer sites decreased slightly in younger women and were stable in younger men, while incidence rates in older men approached or even surpassed that of older women. Data on the current burden showed that cervical precancer and genital warts are still the major contributors to HPV-associated disease, and oropharyngeal cancer now accounts for more annual cases on a population level than cervical cancer. Danish data show decreased incidence of cervical lesions and genital warts in the post-vaccine era. Despite population impact of HPV vaccination, HPV-associated disease remains a public health issue and increasingly among men.

Elimination of cervical cancer: Lessons learned from polio and earlier eradication programs

This paper reviews definitions of control, elimination, and eradication and considers lessons learned from prior and current elimination/eradication efforts that might inform the current effort to eliminate cervical cancer. This task is complicated by the varying definitions of elimination extant. Lessons for cervical cancer elimination notably include the necessity for political will/champions; the need for a specific target with a time span; the need for program efforts to be guided by surveillance of disease and death (not just coverage); the need for accountability, monitoring, and evaluation at all levels; and the need for ongoing research. Although achieving the goal of elimination will be difficult, success will mean the prevention of millions of deaths due to cervical cancer.

Cervical cancer screening by visual inspection and HPV testing in Eswatini

In 2009, visual inspection with acetic acid (VIA) followed by cryotherapy (VIA-and-cryotherapy), was introduced into the Eswatini cervical cancer prevention programme. We present screening results of 654 women attending VIA-and-cryotherapy who participated in a sexually transmitted infections prevalence study, at which samples for HPV DNA testing and liquid-based cytology (LBC) were also collected. VIA positives (VIA+) ineligible for cryotherapy, suspected cancers and women with high-grade squamous intraepithelial or worse lesions (HSIL+) on LBC were referred for diagnosis and treatment. Women with negative VIA who were HPV positive (HPV+) and those VIA+ treated with cryotherapy were recalled for another VIA one-year later. The positivity rates of VIA, HPV, atypical squamous cells of undetermined significance or worse cytology abnormalities (LBC ASCUS+) and low-grade squamous intraepithelial or worse lesions (LBC LSIL+) were 9.7%, 42.6%, 13.2% and 5.3%, respectively. HPV testing detected 29 of 31 LSIL+ (93.6%, 95%CI: 78.6-99.2) while VIA only detected 11 (35.6%, 95%CI: 19.2-54.6). The HIV prevalence was 43% (95%CI: 39.2-46.9). HIV positives were at increased risk of being VIA+ (age-adjusted odds ratio: 2.5, 95%CI: 1.5-4.3), HPV+ (3.7, 2.6-5.3) and having LSIL+ (16.3, 4.9-54.8). The ineligibility rates for cryotherapy were 38% (24 of 63 VIA+), and 46% among HIV positives (18 of 39 VIA+). HPV testing was substantially more sensitive than VIA, thus, HPV followed by ablative treatment may be more effective. However, the high ineligibility for cryotherapy highlights the need for improving the assessment of eligibility for ablative treatment and for strengthening colposcopy, particularly in populations with high HIV prevalence.

Awareness of the link between human papillomavirus and oral cancer in UK university students

Awareness of the link between human papillomavirus (HPV) and oral cancer varies across populations. Levels of awareness and factors may impact HPV vaccine uptake in women and the intent to obtain the vaccine in men if it becomes available. A cross-sectional survey of 1415 UK university students (495 men and 920 women) aged 18-25 years was conducted. Women who had and had not received the HPV vaccine were included. Vaccination was not available for men at the time of the survey. Seventy percent of participants had heard of oral cancer but only 25% were aware of the link between HPV and oral cancer. Women who ever engaged in sexual activity (adjusted odds ratio, aOR = 1.74; 95% CI: 1.12-2.72) or had at least one dose of the HPV vaccine (aOR = 1.71; 95% CI: 1.24-2.37) were more likely to be aware. Men who intend to receive the HPV vaccine in the future were more likely to be aware (aOR = 1.62; 95% CI: 1.04-2.53). Non-white women were less likely to be vaccinated (aOR = 0.56; 95% CI: 0.41-0.77). However, being aware was associated with HPV vaccine uptake in women (aOR = 1.65; 95% CI: 1.19-2.28) and borderline associated with the intent to obtain the HPV vaccine in men (aOR = 1.52; 95% CI: 0.99-2.35). Non-heterosexual men were more willing than heterosexuals to receive the vaccine. Following the UK gender-neutral HPV vaccination programme, there is an opportunity to increase awareness about the link between HPV and oral cancers aside from the cervical cancer link to influence HPV vaccine uptake.

Disability and receipt of the Papanicolaou test for cervical cancer screening: A systematic review and meta-analysis

To synthesize literature comparing Papanicolaou (Pap) test receipt between women with and without disabilities. We searched the following databases from inception to March 1, 2024: OVID Medline (1946-), EBSCO CINAHL Plus (1981-), OVID EMBASE (1974-), and OVID APA PsycINFO (1806-). Eligible studies were peer-reviewed and compared receipt of Pap tests in women with physical, hearing, vision, or intellectual/developmental disability versus those without disabilities. We extracted data using a standardized form; study quality was appraised using the Newcastle-Ottawa Scale; and results were synthesized using random-effects meta-analyses, where possible. Findings that could not be meta-analyzed were summarized following Synthesis Without Meta-analysis guidelines. Grading of Recommendations, Assessment, Development and Evaluation was used to assess the strength of evidence. Of 1946 unique studies screened, 43 were included in the review, and 21 were meta-analyzed. Studies were primarily cross-sectional (65.1 %), used survey data (76.7 %), and were conducted in the United States (60.5 %). Quality was rated high (30.2 %), medium (55.8 %), and low (14.0 %). Women with disabilities had a lower likelihood of receiving a Pap test (adjusted pooled OR 0.78, 95 % CI: 0.66-0.91). Disparities were more pronounced among those with physical (adjusted pooled OR 0.74, 95 % CI: 0.68-0.80) and intellectual/developmental disabilities (adjusted ORs ranging from 0.21 to 0.37). The overall strength of evidence was low. Women with disabilities could benefit from efforts to improve cervical cancer screening receipt. Future studies should continue to explore this association, including using population-based data that may better capture the needs of this group.

Weight discrimination and up-to-date breast and cervical cancer screening in US women

Little research has investigated whether people's experiences with weight-related discrimination serve as a barrier to cancer screening. This study examined the association between weight discrimination and receipt of up to date (UTD) cervical and breast cancer screening in a demographically diverse sample of US women with representation across the body mass index (BMI) spectrum. In 2021, women aged 25-64 years completed an online survey. Multivariable logistic regression assessed the association between perceived weight discrimination (as measured by the Stigmatizing Situations Survey-Brief) and self-reported cervical (N = 909) and breast cancer screening (N = 442), in Black and White women, adjusting for BMI and demographic characteristics. Among White women, more frequent exposure to weight discrimination was associated with significantly lower odds of UTD cervical cancer screening, AOR = 0.78; 95 % CI = 0.62, 0.97, and breast cancer screening, AOR = 0.53, 95 % CI = 0.36, 0.78; for each unit increase on the weight discrimination scale, the odds of screening decreased by approximately 25-50 %. In contrast, weight discrimination was not significantly associated with either type of screening among Black women. Previous experiences with weight discrimination may deter some women from seeking routine cancer screening. Strategies for mitigating the harmful consequences of weight-related discrimination in health care settings are needed.

Cancer screening uptake among refugees in high and middle-income countries: a systematic review

Cancer screening is a crucial strategy for reducing cancer morbidity and mortality. Refugees encounter disproportionate challenges in preventive healthcare, yet their cancer screening uptake remain poorly characterized. We aimed to synthesize breast, cervical, and colorectal cancer screening uptake among refugees in high and middle-income countries. A systematic search was conducted using OVID (Medline, Embase), CINAHL, Web of Science, and Scopus from inception to July 2024 to identify studies reporting breast, cervical, and colorectal cancer screening uptake among refugees. Articles were screened in Covidence, and methodological quality was assessed using the Joanna Briggs Institute checklist. Data were synthesized with a descriptive and narrative approach. Of 2044 articles retrieved, 23 studies included in the review. Refugees exhibited lower cervical, breast, and colorectal cancer screening uptake than non-refugees with variation across cancer types. Reported rates of ever having Pap test and mammogram among refugee women ranged from 13.9 % to 59 %, and 5.3 % to 63 %, respectively. Commonly cited determinants of cancer screening uptake included education, length of stay, cultural/religious beliefs, and family/provider recommendations. Refugees had lower cancer screening uptake than host populations. Targeted, culturally informed multilevel interventions addressing their unique barriers are needed to improve refugees access to cancer screening.

The association of childhood experiences of abuse on timely cervical cancer screening utilization among women in the United States

Cervical cancer remains a significant public health concern, particularly among vulnerable populations. This study examines the association between Adverse Childhood Experiences (ACEs) and timely Pap test utilization for cervical cancer screening among women aged 21-65 years, with a focus on the association of abuse. This study utilized the 2020 Behavioral Risk Factor Surveillance System (BRFSS) that included 41,111 women aged 21-65 years from 29 states. Using descriptive analysis and multivariable logistic regression, we conducted exploratory analyses to assess the association between experiences of abuse and timely Pap test utilization and to examine if household challenges moderate this association. Women who did not experience abuse had higher odds of receiving a timely Pap test compared to those with a history of abuse (aOR = 1.29, 95 % CI: 1.08-1.54). While household challenges were not significantly associated with timely screenings (aOR = 0.84, 95 % CI: 0.71-1.01), women without household challenges and abuse had significantly higher odds of receiving timely Pap tests (aOR = 1.66, 95 % CI: 1.27-2.17). Non-Hispanic Black women, married women, women with higher education, women who were employed, and women who had health insurance showed higher odds of timely Pap test utilization. The study highlights the association between ACEs and preventive health behaviors. These findings emphasize the need for trauma-informed care interventions to address these disparities. Policy recommendations include expanding and enhancing access to cervical cancer screening for women with ACEs.

International Papillomavirus Society policy statement on human papillomavirus-based cervical cancer screening for women living with HIV

Women living with HIV (WLWH) are among those at highest risk for cervical cancer development, thereby making this a key population for primary and secondary prevention. Human papillomavirus (HPV) nucleic acid (DNA or RNA) tests, which have been clinically validated, are supported by the World Health Organization (WHO) as the preferred method for cervical screening for all women, although HPV DNA is preferred in WLWH until further evidence demonstrates that HPV RNA is equivalent. We sought to describe current guidelines for HPV-based cervical cancer screening for WLWH. This paper outlines current recommendations and the state of knowledge regarding HPV-based cervical cancer screening for WLWH. Current recommendations and the state of knowledge have been subdivided into the following topics: cervical screening and triage; treatment; additional considerations; and challenges and opportunities. The International Papillomavirus Society supports the WHO recommendations regarding HPV-based screening for all women, including WLWH. As data to support best practices in WLWH are limited, we strongly encourage continued research into this important topic.

Cervical cancer screening and risk factor prevalence by sexual identity: A comparison across three national surveys in the United States

Women identifying as lesbian, gay, bisexual, or queer (LGBQ) have lower cervical cancer screening use and differences in care access. Less known about how differences vary by data sources and within LGBQ subgroups. We evaluated LGBQ disparities in cervical cancer screening use and risk factors across three national surveys in the United States. Data were from the 2019 and 2021 National Health Interview Survey, the 2018 and 2020 Behavioral Risk Factor Surveillance Survey, and the 2017-2019 National Survey of Family Growth. We meta-analyzed self-reported cervical cancer screening to estimate pooled relative risks (pRR), comparing those identifying as LGBQ to those identifying as straight/heterosexual. We also evaluated differences in care access and behavioral risk factors by sexual identity. Despite demographic differences across surveys, all three surveys demonstrated a small reduction in up-to-date cervical cancer screening for LGBQ vs. straight/heterosexual women (pRR = 0.91 [CI 0.89-0.93]). The screening gap was larger for gay/lesbian (pRR: 0.90 [0.85-0.94]) than bisexual women (pRR: 0.94 [0.92-0.97]) and largest at younger ages (pRR age 21-29: 0.89 [CI 0.85-0.93]). LGBQ women reported consistently lower access to care across multiple measures. Risk factors were mixed, including higher smoking rates and higher HPV vaccination coverage for LGBQ women vs. straight. LGBQ women are less likely to be screened for cervical cancer. Closing disparities in care access and identifying feasible and acceptable screening interventions will help reduce these disparities. We must also ensure high-quality data collection to monitor disparities across and within key subgroups.

Decreasing participation in Dutch population-based cancer screening programs: Trends from 2018 to 2022

Population-based screening programs for breast, cervical, and colorectal cancer have been proven effective in detecting cancer at an early or precancerous stage, thereby enabling better patient outcomes. For screening programs to remain effective at a population level, high participation rates are essential. Data on participation in the three nationwide screening programs in the Netherlands from 2018 to 2022 were obtained from the national screening information system (ScreenIT). Participation rates were calculated to assess trends over time, stratified by invitation round (first vs. subsequent) and sex (for colorectal cancer only). Participation was consistently lower for the first invitation rounds and men compared to subsequent rounds and women. Decreasing participation rates were observed for all programs and subgroups. In five years' time, overall participation decreased from 76.9 % to 70.7 % for breast cancer (-8.0 %), 55.5 % to 48.6 % for cervical cancer (-12.4 %), and 73.0 % to 68.4 % for colorectal cancer (-6.2 %). While some logistical factors may have contributed to decreasing participation rates, the consistent decline observed across all three nationwide screening programs remains unclarified. Our results emphasize that continuous monitoring of screening programs is crucial, and accessibility of cancer screening should be prioritized.

U.S. national trends in cervical cancer screening by sexual orientation and race/ethnicity in cisgender women

Changes in up-to-date cervical cancer screening (CCS) over time by sexual orientation and race/ethnicity were estimated to identify trends in screening disparities. This 2024 retrospective, cross-sectional analysis of National Health Interview Survey data (years 2013, 2015, 2019 and 2021) included 40,818 cisgender women aged 21-65 without hysterectomy. Joinpoint analysis was performed to calculate the annual percent change (APC) of up-to-date CCS from 2013 to 2021. Logistic regression (years 2019 and 2021) was used to describe the relationship between up-to-date screening and sexual orientation, race/ethnicity, and the interaction thereof. The adjusted odds of up-to-date CCS were 22 % lower for lesbian, gay, and/or bisexual (LGB) compared to heterosexual women (OR = 0.78, p = 0.01). Up-to-date CCS fell significantly from 80.50 % in 2013 to 75.00 % in 2021 for heterosexual respondents (APC = -0.97 %, p < 0.01), but was stable across years for LGB respondents. Up-to-date CCS decreased for Hispanic (APC = -1.52, p < 01) and non-Hispanic White only heterosexual women (APC = -0.63, p = 0.02). It also decreased for non-Hispanic Black/African American only LGB women (APC = -2.67, p < 0.01) falling from 85.22 % in 2013 to 67.91 % in 2021. By multiplicative interaction, LGB Hispanic women were more up-to-date than their heterosexual counterparts (p = 0.05). In 2021 there were approximately 19.72 million women aged 21-65 who were not up-to-date with CCS. 1.76 million LGB women were not up-to-date for CCS, and a greater proportion of these women identified as non-Hispanic Black/African American. CCS must be improved for all cisgender women, and specific attention should be given to those who identify as LGB and/or Black/African American.

Response letter to “Understanding the age-related epithelial shifts at the uterine cervix and the area of risk for squamous cell cervical cancer”

Understanding the age-related epithelial shifts at the uterine cervix and the area of risk for squamous cell cervical cancer

Using electronic health records to evaluate the adherence to cervical cancer prevention guidelines: A cross-sectional study

The fight against cervical cancer requires effective screening together with optimal and on-time treatment along the care continuum. We examined the impact of cervical cancer testing and treatment guidelines on testing practices, and follow-up adherence to guidelines. Data from Estonian electronic health records and healthcare provision claims for 50,702 women was used. The annual rates of PAP tests, HPV tests and colposcopies during two guideline periods (2nd version 2012-2014 vs 3rd version 2016-2019) were compared. To assess the adherence to guidelines, the subjects were classified as adherent, over- or undertested based on the timing of the appropriate follow-up test. The number of PAP tests decreased and HPV tests increased during the 3rd guideline period (p < 0.01). During the 3rd guideline period, among 21-29-year-old women, the adherence to guidelines ranged from 38.7% (44.4…50.1) for ASC-US to 73.4% (62.6…84.3) for HSIL and among 30-59-year-old from 49.0% (45.9…52.2) for ASC-US to 65.7% (58.8…72.7) for ASCH. The highest rate of undertested women was for ASC-US (21-29y: 25.7%; 30-59y: 21.9%). The rates of over-tested women remained below 12% for all cervical pathologies observed. There were 55.2% (95% CI 49.7…60.8) of 21-24-year-olds and 57.1% (95% CI 53.6…60.6) of 25-29-year-old women who received HPV test not adherent to guidelines. Our findings highlighted some shortcomings in guideline adherence, especially among women under 30. The insights gained from this study help to improve the quality of care and, thus, reduce cervical cancer incidence and mortality.

Prevalence of cervical human papillomavirus in kidney transplant recipients: A systematic review and meta-analysis

This systematic review and meta-analysis aims to investigate the prevalence of cervical high-risk human papillomavirus (hrHPV) among kidney transplant recipients (KTRs) and, furthermore to compare it to that in immunocompetent controls. A systematic literature search was conducted in PubMed, EMBASE, and Cochrane Library databases from January 2000 to February 2023, to identify studies investigating the prevalence of cervical hrHPV in KTRs. Pooled cervical hrHPV prevalences, odds ratios (ORs) comparing KTRs to controls and corresponding confidence intervals (CIs) were estimated using random effects logistic regression models. Heterogeneity between studies was assessed through the I Altogether, 16 studies covering >1200 KTRs were included. The prevalence of cervical hrHPV in KTRs was 27.7% (95% CI 21.3-35.1) with substantial interstudy heterogeneity. Stratification indicated a higher prevalence in recent years (2019-2023) and in Asia (39% (95% CI 11.2-61.4)). The prevalence of HPV16 and HPV18 in KTRs was 8.0% (95% CI 3.9-15.9) and 1.7% (95% CI 0.8-3.7), respectively. Comparing hrHPV prevalence in KTRs and controls based on six studies including >500 KTRs and 1000 controls, the OR for hrHPV was 2.0 (95% CI 1.1-3.6). This meta-analysis establishes an increased cervical hrHPV prevalence in KTRs compared to controls. The increased risk may be associated with immunosuppressive therapy post-transplantation. Further research is needed to explore the potential benefits of HPV vaccination, including potential revaccination strategies in KTRs.

Squamocolumnar junction visibility among cervical cancer screening population in Peru might influence upper age for screening programs

Cervical cancer screening and treatment of screen positives is an important and effective strategy to reduce cervical cancer morbidity and mortality. In order to have an accurate cervical cancer screening and evaluation of positives, the entire Squamocolumnar Junction (SCJ) must be visible. Throughout the life course, the position of the SCJ changes and affects its visibility. SCJ visibility was analyzed among participants screened at the League Against Cancer Clinic in Lima, Peru. Of the 4247 participants screened, the SCJ was fully visible in 49.7% of participants, partially visible in 23.1%, and not visible in 27.2%. Visibility decreased with age, and by age 45 years old, the SCJ was not fully visible in over 50% of participants. Our results show that a high percentage of participants at ages still recommended for screening do not have totally visible SCJ, and we may need to reconsider the upper age limit for screening and find new strategies for evaluation of those with a positive screening test and non-visible SCJ.

Social media use in HPV-, cervical cancer-, and cervical screening-related research: A scoping review

In response to the World Health Organization's global call to eliminate cervical cancer, many countries have targets to implement human papillomavirus (HPV) primary screening. Social media may offer opportunities to promote uptake of HPV screening. We aimed to describe the extent of the scientific literature regarding social media research on HPV, cervical cancer and cervical screening. Seven databases were searched for peer-reviewed English-language studies related to social media research and HPV, cervical cancer and cervical screening published up to November 2023. One reviewer completed the title/abstract screening and two reviewers independently reviewed full-text articles. Data extraction was carried out by one reviewer and verified by a second reviewer. Information such as the research topic, social media platform of interest, participant characteristics, methods, analysis type, outcome measures, and key findings were collected. In the 58 articles included, researchers used social media in the following ways: evaluate content, recruit participants or disseminate a survey/questionnaire, disseminate health communication content, examine the relationship between social media use and outcomes, and to conduct experiments testing the effects of social media content on outcomes. Twitter and Facebook were the most common platforms mentioned. Four articles explicitly mentioned theory. Opportunities for research are identified such as further exploration of how newer social media platforms such as Instagram and TikTok can be used to share HPV content, examination of appropriate images for effective communication, and determining key features of social media content to promote information sharing and improve cervical screening knowledge, attitudes and behaviours.

Association between long working hours and engagement in preventive healthcare services in Korean workers: Findings from the Korean National Health and Nutrition Examination Survey

Engagement in preventive healthcare services is crucial for preventing diseases. We explored how working hours are associated with engagement in preventive healthcare services, with a focus on gender differences. This cross-sectional study used data from the 2007-2012 Korean National Health and Nutrition Examination Survey. The dependent variable was engagement in each of the five preventive healthcare services (health check-ups, influenza vaccination, and stomach, breast, and cervical cancer screenings). We estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs) using robust Poisson regression. The study analyzed 19,819 workers (9119 women). The adjusted PRs (95% CI) of the association between working ≥55 h per week and engagement in preventive healthcare services among men were 0.95 (0.90-1.00) for health check-ups, 0.86 (0.77-0.96) for influenza vaccination, and 0.95 (0.87-1.03) for stomach cancer screening compared to working 35-40 h per week. Among women, the adjusted PRs (95% CI) of the association between working ≥55 h per week and engagement in preventive healthcare services were 0.84 (0.78-0.91) for health check-ups, 0.82 (0.73-0.92) for influenza vaccination, and 0.88 (0.80-0.97) for stomach, 0.85 (0.78-0.94) for breast, and 0.82 (0.74-0.91) for cervical cancer screenings. Long working hours were negatively associated with engagement in preventive healthcare services, and the association was pronounced among female workers. Efforts to promote preventive healthcare participation among individuals with long working hours are necessary, and it is essential to consider the unique vulnerabilities of women when developing such policies.

Evaluating the cost-effectiveness of HPV vaccination for adolescent girls in Japan: A comparison of 2-valent, 4-valent, and 9-valent HPV vaccines with consideration of cross-protection

In April 2023, the Japanese Health Ministry panel approved the inclusion of the 9-valent human papillomavirus (9vHPV) vaccine in the National Immunization Program, alongside the 2-valent (2vHPV) and 4-valent HPV (4vHPV) vaccines. In response to this, we evaluated the cost-effectiveness of these three vaccines for routine immunization of girls aged 12-16 in Japan, considering the cross-protection of 2vHPV and 4vHPV vaccines. We constructed an age-structured mathematical model for HPV transmission, aiming to quantify the economic and epidemiological effects of various HPV vaccination strategies over a 70-year period in Japan. We determined incremental costs and quality-adjusted life years (QALYs) for each strategy, applying a 3% annual discount. Univariate and probabilistic sensitivity analyses were conducted to assess the uncertainty of our model results, with all evaluations done in 2023. Our projections indicate that the HPV vaccination program in Japan will significantly reduce the incidence of HPV-related diseases. All HPV vaccination strategies, using the 2vHPV, 4vHPV, and 9vHPV vaccines, were found to be cost-effective compared to no vaccination, with incremental cost-effectiveness ratios of ¥971,447/QALY, ¥1,237,297/QALY, and ¥742,084/QALY, respectively. Direct comparisons between vaccines demonstrated that the 9vHPV vaccination was more cost-effective than the 2vHPV vaccination, whereas 4vHPV vaccination was dominated by 2vHPV vaccination. Our study validates the cost-effectiveness of implementing the 9vHPV vaccine as the primary option over the 2vHPV or 4vHPV vaccine for girls in Japan. These findings underscore the need to improve the acceptance rate and coverage of HPV vaccinations in the country.

A population-based survey of self-reported delays in breast, cervical, colorectal and lung cancer screening

The early COVID-19 pandemic was associated with cessation of screening services, but the prevalence of ongoing delays in cancer screening into the third year of the pandemic are not well-characterized. In February/March 2022, a population-based survey assessed cancer needs in New Hampshire and Vermont. The associations between cancer screening delays (breast, cervical, colorectal or lung cancer) and social determinants of health, health care access, and cancer attitudes and beliefs were tested. Distributions and Rao-Scott chi-square tests were used for hypothesis testing and weighted to represent state populations. Of 1717 participants, 55% resided in rural areas, 96% identified as White race, 50% were women, 36% had high school or less education. Screening delays were reported for breast cancer (28%), cervical cancer (30%), colorectal cancer (24%), and lung cancer (30%). Delays were associated with having higher educational attainment (lung), urban living (colorectal), and having Medicaid insurance (breast, cervical). Low confidence in ability to obtain information about cancer was associated with screening delays across screening types. The most common reason for delay was the perception that the screening test was not urgent (31% breast, 30% cervical, 28% colorectal). Cost was the most common reason for delayed lung cancer screening (36%). COVID-19 was indicated as a delay reason in 15-29% of respondents; 12-20% reported health system capacity during the pandemic as a reason for delay, depending on screening type. Interventions that address sub-populations and reasons for screening delays are needed to mitigate the impact of the COVID-19 pandemic on cancer burden and mortality.

The impact of a universal human papilloma virus (HPV) vaccination program on lower genital tract dysplasia and genital warts

Assess Ontario's school-based human papillomavirus (HPV) vaccination program on reducing rates of cervical dysplasia, colposcopy services and treatment for genital warts, cervical conization, cryotherapy and laser vaporization of the lower genital tract. Women born in 1995 in Ontario, Canada were the first cohort of students to receive the vaccine. We followed these women from age 18-23 and identified pap test cytology results, referral and attendance at colposcopy, treatment of HPV related warts and treatment of lower-genital tract dysplasia using administrative databases. We compared the incidence of these outcomes to women born in 1985, followed during the same age period prior to access to the HPV vaccine. We calculated relative risk ratios for all outcomes over the 5-year period for the unvaccinated group compared to the vaccinated group. Results were stratified at the income and geographic level. A total of 221,039 women were included. Among vaccinated women, 5.2% percent had cytologic abnormalities and 2.7% required treatment for pre-invasive disease or warts compared to 9.2% and 5.2%, respectively among unvaccinated women. The relative risk of developing a low-grade cytologic abnormality if unvaccinated was 1.69 and 3.74 for high-grade abnormalities. The relative risk of requiring colposcopy if unvaccinated was 1.94 and they were 6.15 times more likely to require treatment. There were no differences between socio-economic groups and geographic regions. Vaccination programs are effective at decreasing rates of cervical dysplasia, lead to reduced need for colposcopy, treatment of HPV related warts and pre-invasive disease even at early ages.

Cervical screening in high-income countries: the need for quality assurance, adjunct biomarkers and rational adaptation to HPV vaccination

We here discuss human papillomavirus (HPV)-based screening avenues to achieve elimination of cervical cancer as a public health problem in high-income country (HIC) settings, covering both the most recent data on the performance of HPV testing, as well as the currently most robust triage methods that are known. We also provide an outlook to several other promising, yet not fully established, options for triage that have been proposed, including methylation, dual staining, machine learning, and artificial intelligence. Finally, we discuss the key issue of how to adapt screening in the presence of programmatic HPV vaccination, and how this combination can best be leveraged for comprehensive cancer control. We conclude that, for the HIC setting, evidence-based and effective cervical screening methods are readily available, but whichever method or platform is chosen, we would propose that recurring audits of performance and population attendance remain common denominators for maintaining successful disease prevention.

Stigma and cervical cancer prevention: A scoping review of the U.S. literature

Cervical cancer is preventable through HPV vaccination and screening however, uptake falls below national targets. A scoping review was conducted to describe stigmas related to HPV infection and vaccination and cervical cancer and screening in the US. Results were organized into the domains proposed by Stangl and colleagues' Health Stigma and Discrimination Framework. Common drivers of stigma were fear of social judgement and rejection, self-blame, and shame. Positive facilitators included social norms that provided motivation to receive HPV vaccination and screening. Gender and social norms were notable negative facilitators of stigma. HPV infection and cervical cancer resulted in stigma marking through the belief that both result from incautious behavior-either multiple sexual partners or failing to get screening. Stereotyping and prejudice were stigma practices attributed to HPV infection and cervical cancer through these same behaviors. Stigma experiences related to HPV infection, cervical cancer, and abnormal screening results included altered self-image based on perceived/anticipated stigma, as well as discrimination. This review advances understanding of the multiple dimensions of stigma associated with these outcomes in the US population. Three areas warrant additional consideration. Future studies should 1) assess how stigma dimensions affect uptake of cervical cancer preventions efforts; 2) focus on US women most affected by cervical cancer incidence and mortality to identify potential differences in these dimensions and tailor interventions accordingly; 3) include women from geographic areas of the US with high rates of cervical cancer to adapt interventions that address potential regional variations in resources and need.

Factors associated with participation in the organized cervical cancer screening program in the greater Paris area (France): An analysis among more than 200,000 women

We aimed to identify the contextual factors associated with participation in the organized Cervical Cancer Screening (CCS) pilot program, which includes specific interventions to reach vulnerable women, in the Greater Paris region. Study population consisted of 231,712 women aged 25-65 years, who were not up to date to their smear test and had been invited to take part in the program from July 2014 to September 2017. Using a multilevel mixed logistic regression with random effects, we investigated the effect of grassroots interventions targeting vulnerable women, healthcare provider accessibility, social environment and municipal policy-related factors. The CCS rate was two times higher in women who had received their first invitation to the program during the study period (32·9%) compared to those who were already invited before the study period (15·3%). In both populations, there were no significant trends in participation with regards to the type of grassroots interventions, level of accessibility of healthcare services or municipal commitment to healthcare. Among women invited previously and aged above 35 increased participation was seen in neighborhoods with low proportion of single women or in less deprived neighborhoods. Our results identified groups of women who participated less in the organized CCS program and suggested that additional interventions targeting the barriers faced by vulnerable women, especially those aged 35-45 years old, are needed.

Given a choice between self-sampling at home for HPV testing and standard of care screening at the clinic, what do African American women choose? Findings from a group randomized controlled trial

The goals of this study were to: (1) evaluate adherence to cervical cancer screening using a patient-centered approach that provided a choice of self-sampling at home for human papillomavirus (HPV) testing or standard of care screening at the local health department ('Choice') versus only standard of care screening at the local health department ('SCS') among un/under-screened African-American women; and (2) examine whether women given a choice were more likely to choose and adhere to self-sampling for HPV testing. We conducted a group randomized trial among un/under-screened African-American women in the Mississippi Delta, with "town" as the unit of randomization (12 towns). Both interventions (i.e., 'Choice' versus 'SCS') were delivered by Community Health Workers (CHWs) through a door-to-door approach. A total of 335 women were enrolled in the study from 2016 to 2019. The 'Choice' arm had a significantly (p = 0.005) higher adherence to screening compared to the 'SCS' arm after adjusting for the cluster effect and other relevant behavioral variables. Participants in the 'Choice' arm were 5.62 (95% CI 1.71-18.44) times more likely to adhere to cervical cancer screening compared to participants in the 'SCS' arm. Women in the 'Choice' arm were significantly more likely to choose (76%) and adhere to self-sampling at home for HPV testing (48% adherence) compared to standard of care screening at the local health department (7.5% adherence). A theory-driven, CHW-led intervention can effectively promote cervical cancer screening among un/under-screened African-American women in a rural setting when women are provided with a choice between two screening modalities. Clinical Trials Registration: NCT03713710.

COVID-19 impact on screening test volume through the National Breast and Cervical Cancer early detection program, January–June 2020, in the United States

Women from racial and ethnic minority groups face a disproportionate burden of cervical and breast cancers in the United States. The Coronavirus Disease 2019 (COVID-19) pandemic might exacerbate these disparities as supply and demand for screening services are reduced. The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides cancer screening services to women with low income and inadequate health insurance. We examined COVID-19's impact on NBCCEDP screening services during January-June 2020. We found the total number of NBCCEDP-funded breast and cervical cancer screening tests declined by 87% and 84%, respectively, during April 2020 compared with the previous 5-year averages for that month. The extent of declines varied by geography, race/ethnicity, and rurality. In April 2020, screening test volume declined most severely in Health and Human Services Region 2 - New York (96% for breast, 95% for cervical cancer screening) compared to the previous 5-year averages. The greatest declines were among American Indian/Alaskan Native women for breast cancer screening (98%) and Asian Pacific Islander women for cervical cancer screening (92%). Test volume began to recover in May and, by June 2020, NBCCEDP breast and cervical cancer screening test volume was 39% and 40% below the 5-year average for that month, respectively. However, breast cancer screening remained over 50% below the 5-year average among women in rural areas. NBCCEDP programs reported assisting health care providers resume screening.

De-implementation of cervical cancer screening before age 21

In 2012, United States consensus guidelines were modified to recommend that cervical cancer screening not begin before age 21 and, since 2014, the Health Effectiveness Data and Information Set (HEDIS), a health plan quality measurement too, has included a measure for non-recommended cervical cancer screening among females ages 16-20. Our goal was to describe prevalence over time of cervical cancer screening before age 21 following the 2012 guideline change, and provide information to help understand how rapidly new guidelines may be disseminated and implemented into clinical practice. We used longitudinal clinical and administrative data from three diverse healthcare systems in the Population-based Research to Optimize the Screening Process (PROSPR II) consortium to examine annual trends in screening before age 21. We identified 55,316 average-risk, screening-eligible females ages 18-20 between 2011 and 2017. For each calendar year, we estimated the proportion of females who received a Papanicolaou (Pap) test. We observed a steady decline in the proportion of females under age 21 who received a Pap test, from an average of 8.3% in 2011 to <1% in 2017 across the sites. The observed steady decline suggests growing adherence to the 2012 consensus guidelines. This trend was consistent across diverse geographic regions, healthcare systems, and patient populations, strengthening the generalizability of the results; however, since we only had 1-2 years of study data prior to the consensus guidelines, we cannot discern whether screening under age 21 was already in decline. Nonetheless, these results provide data to compare with other guideline changes to de-implement non-recommended screening practices.

Accuracy of combined molecular and morphology-based triage for HPV-positive women in routine cervical cancer screening services from Colombia

WHO cervical cancer elimination goals comprise 70% of highly-sensitive screening coverage and 90% treatment of precancerous lesions. Triage for HPV-positive women may challenge sensitivity of screening algorithms and women's follow-up, particularly in low- and middle-income countries (LMIC) where screening quality and protocol adherence are frequently deficient. We aimed to determine the accuracy of triage for HPV positive women in routine screening services from Colombia by a prospective cross-sectional study. Consecutively, HPV DNA-positive women underwent six triage strategies (conventional cytology, two methods of visual inspection, HPV16/18/45-genotyping, telomerase, and HPV mRNA). Positive triage results underwent regular colposcopy/biopsy in public hospitals. Adjusted sensitivity, specificity, and predictive values for CIN2+/CIN3+ were estimated for stand-alone and combined tests. We explored the impact of triage strategies on referral rates and the complete screening algorithm (screening plus triage). Overall 16,242 women underwent HPV screening and 1789 (11.0%) were HPV-positive. In total, 20.1% of women were lost to follow-up. mRNA showed the highest positivity rate (0.64 among HPV-positive and 0.05 among the total screened cohort), the highest sensitivity (0.94 95%CI 0.75-0.96), and the lowest specificity (0.36 95%CI 0.29-0.43). Parallel testing with HPV-mRNA revealed the highest increase in sensitivity for all triage strategies. Accuracy of cytology and visual inspection differ between screening units but parallel testing with HPV16/18/45 genotyping significantly increased their sensitivity (over 0.80). Morphology-based triage for HPV-positive women remains a suitable alternative for routine practice in LMIC if combined with HPV16/18/45-genotyping; however, point-of-care triage would be preferable to reduce losses to follow-up. HPV-mRNA triage deserves cost-benefit analyses.

Follow-up after abnormal cervical cancer screening in immigrants compared with Danish-born women – A nationwide register study

Cervical cancer screening is offered free-of-charge to women aged 23-64 years in Denmark. Immigrants participate less in screening than Danish-born women, but little is known about their participation in follow-up after abnormal screening results. In this registry-based cohort study, we examined the likelihood of timely follow-up after an abnormal cervical cytology in immigrants from different countries and regions compared with Danish-born women. In nationwide registers, we identified women aged 23-64 years with high-grade (n = 74,335) or low-grade (n = 174,038) abnormal cytology during 1997-2017. Timely follow-up was defined as a new examination within six months for high-grade and 18 months for low-grade abnormalities. We calculated the probability of timely follow-up by country and region of origin and estimated odds ratios (ORs) of timely follow-up between immigrants and Danish-born women. The proportions with timely follow-up after high-grade abnormalities ranged from 90.6%-95.1% in immigrants from different countries or regions, compared with 95.5% in Danish-born women. For low-grade abnormalities, follow-up ranged from 75.2%-92.8% in immigrants, compared with 90.6% in Danish-born women. Women from Sub-Saharan Africa had low probability of timely follow-up after both high-grade (90.9%) and low-grade (75.2%) abnormalities. The differences between immigrants and Danish-born women remained when adjusting for age, year, income, employment and marital status. In conclusion, immigrants from most countries and regions were slightly less likely than Danish-born women to receive timely follow-up after abnormal cervical cytology, also after adjusting for socioeconomic differences. Efforts should be made to improve follow-up of abnormal screening results in immigrant groups with low attendance.

Cost-effectiveness of nonavalent HPV vaccine in Norway considering current empirical data and validation

Impact of COVID-19 on cervical cancer screening: Challenges and opportunities to improving resilience and reduce disparities

The COVID-19 pandemic has a major impact on a wide range of health outcomes. Disruptions of elective health services related to cervical screening, management of abnormal screening test results, and treatment of precancers, may lead to increases in cervical cancer incidence and exacerbate existing health disparities. Modeling studies suggest that a short delay of cervical screening in subjects with previously negative HPV results has minor effects on cancer outcomes, while delay of management and treatment can lead to larger increases in cervical cancer. Several approaches can mitigate the effects of disruption of cervical screening and management. HPV-based screening has higher accuracy compared to cytology, and a negative HPV result provides longer reassurance against cervical cancer; further, HPV testing can be conducted from self-collected specimens. Self-collection expands the reach of screening to underserved populations who currently do not participate in screening. Self-collection and can also provide alternative screening approaches during the pandemic because testing can be supported by telehealth and specimens collected in the home, substantially reducing patient-provider contact and risk of COVID-19 exposure, and also expanding the reach of catch-up services to address backlogs of screening tests that accumulated during the pandemic. Risk-based management allows prioritizing management of patients at highest risk of cervical cancer while extending screening intervals for those at lowest risk. The pandemic provides important lessons for how to make cervical screening more resilient to disruptions and how to reduce cervical cancer disparities that may be exacerbated due to disruptions of health services.

Measuring the impact of the COVID-19 pandemic on organized cancer screening and diagnostic follow-up care in Ontario, Canada: A provincial, population-based study

It is essential to quantify the impacts of the COVID-19 pandemic on cancer screening, including for vulnerable sub-populations, to inform the development of evidence-based, targeted pandemic recovery strategies. We undertook a population-based retrospective observational study in Ontario, Canada to assess the impact of the pandemic on organized cancer screening and diagnostic services, and assess whether patterns of cancer screening service use and diagnostic delay differ across population sub-groups during the pandemic. Provincial health databases were used to identify age-eligible individuals who participated in one or more of Ontario's breast, cervical, colorectal, and lung cancer screening programs from January 1, 2019-December 31, 2020. Ontario's screening programs delivered 951,000 (-41%) fewer screening tests in 2020 than in 2019 and volumes for most programs remained more than 20% below historical levels by the end of 2020. A smaller percentage of cervical screening participants were older (50-59 and 60-69 years) during the pandemic when compared with 2019. Individuals in the oldest age groups and in lower-income neighborhoods were significantly more likely to experience diagnostic delay following an abnormal breast, cervical, or colorectal cancer screening test during the pandemic, and individuals with a high probability of living on a First Nation reserve were significantly more likely to experience diagnostic delay following an abnormal fecal test. Ongoing monitoring and management of backlogs must continue. Further evaluation is required to identify populations for whom access to cancer screening and diagnostic care has been disproportionately impacted and quantify impacts of these service disruptions on cancer incidence, stage, and mortality. This information is critical to pandemic recovery efforts that are aimed at achieving equitable and timely access to cancer screening-related care.

Prioritizing cervical cancer screening services during the COVID-19 pandemic: Response of an academic medical center and a public safety net hospital in California

The expeditious diagnosis and treatment of high-grade cervical precancers are fundamental to cervical cancer prevention. However, during the COVID-19 pandemic healthcare systems have at times restricted in-person visits to those deemed urgent. Professional societies provided some guidance to clinicians regarding ways in which traditional cervical cancer screening might be modified, but many gaps remained. To address these gaps, leaders of screening programs at an academic medical center and an urban safety net hospital in California formed a rapid-action committee to provide guidance to its practitioners. Patients were divided into 6 categories corresponding to various stages in the screening process and ranked by risk of underlying high-grade cervical precancer and cancer. Tiers corresponding to the intensity of the local pandemic were constructed, and clinical delays were lengthened for the lowest-risk patients as tiers escalated. The final product was a management grid designed to escalate and de-escalate with changes in the local epidemiology of the COVID-19 pandemic. While this effort resulted in substantial delays in clinical screening services as mandated by the healthcare systems, the population effects of delaying on both cervical cancer outcomes as well as the beneficial effects related to decreasing transmission of severe acute respiratory coronavirus 2 have yet to be elucidated.

COVID-19 and cancer screening in Scotland: A national and coordinated approach to minimising harm

Screening is an important component of cancer control internationally. In Scotland, the National Health Service Scotland provides screening programmes for cervical, bowel and breast cancers. The COVID-19 pandemic resulted in the suspension of these programmes in March 2020. We describe the integrated approach to managing the impact of the pandemic on cancer screening programmes in Scotland throughout 2020. We outline the policy context and decision-making process leading to suspension, and the criteria and framework informing the subsequent, staggered, restart in subsequent months. The decision to suspend screening services in order to protect screening invitees and staff, and manage NHS capacity, was made after review of numbers of screening participants likely to be affected, and the potential number of delayed cancer diagnoses. Restart principles and a detailed route map plan were developed for each programme, seeking to ensure broad consistency of approach across the programmes and nationally. Early data indicates bowel, breast and cervical screening participation has increased since restart. Primary care has had to adapt to new infection prevention control measures for delivery of cervical screening. Cancer charities provided cancer intelligence and policy briefs to national bodies and Scottish Government, as well as supporting the public, patients and screening invitees through information and awareness campaigns. Emerging from the pandemic, there is recognition of the need and the opportunity to transform and renew both cancer and screening services in Scotland, and in particular to address long-standing workforce capacity problems through innovation and investment, and to continue to prioritise addressing health inequalities.

Treatment approaches for women with positive cervical screening results in low-and middle-income countries

The primary goal of cervical screening is to identify women with cervical precancers who need treatment to prevent invasive cervical cancer. Cervical cancer screening programs in high-resource settings rely on a multi-step process to reassure the majority of women of low cancer risk and treat the small number of women at high risk of precancer and cancer. The requirement of major resource investment for training and capacity building of multi-step cervical cancer screening programs prevents their introduction in low- and middle-income countries (LMICs). Screen-and-treat programs have been evaluated and introduced in some countries that use mainly ablative treatment as primary treatment options. Ablative treatment with cryotherapy and thermal ablation has a favorable tradeoff of benefits and harms and can be introduced more widely than excisional treatment in LMICs. While most women below 40 are eligible for ablative procedures, fewer than 50% are eligible by age 50 and ablative treatment is not appropriate over age 50. Excisional treatment is required for women ineligible for ablative treatment. Since screening programs in LMICs necessarily detect invasive cancers, cancer treatment and palliative care needs to be considered as well.

Current and future vaccine clinical research with the licensed 2-, 4-, and 9-valent VLP HPV vaccines: What's ongoing, what's needed?

Prophylactic HPV vaccination has been a great public health success. For >20 years, clinical trials were conducted with the 2-, 4-, and/or 9-valent vaccines in young-adult females, mid-adult women, males, and adolescents. In all studies, the vaccines were highly efficacious, immunogenic, and well tolerated. Following vaccine licensure and utilization in national vaccine programs globally (real-world settings primarily in high income countries), numerous studies demonstrated that the vaccines continue to have an excellent safety profile and have dramatically reduced the incidence of genital warts, HPV vaccine-type prevalence, and precancerous lesions. Thirty-eight clinical trials with the currently licensed HPV vaccines are ongoing. Key questions being addressed in new trials include: efficacy against persistent infection and immunogenicity of a 1-dose regimen; efficacy of 3 doses in 20-45-year-old females; use in postpartum women and immunocompromised individuals (HIV, liver and kidney transplants); dose sparing via intradermal administration; use in combination with a PD1 monoclonal antibody in patients with cervical cancer; impact on recurrent disease in women undergoing cervical conization; persistence of protection; and use to prevent oropharyngeal cancer. Additional clinical research that should be conducted includes: long-term follow-up, particularly of 1- and 2-dose regimens; further evaluation of flexible 2-dose regimens; immunogenicity of 1- or 2-dose regimens in persons ≥15 years old and immunocompromised populations; safety and immunogenicity of 1 or 2 doses in children <9 years old; assessment of the vaccine in the prevention of transmission; interchangeability with newer HPV vaccines; additional concomitant use studies; and prevention of penile cancer and recurrent respiratory papillomatosis.

Monitoring HPV vaccine impact on cervical disease: Status and future directions for the era of cervical cancer elimination

Post-licensure monitoring of the impact of HPV vaccines is critical to track the progress being made toward cervical cancer elimination and to identify areas where further progress can accelerate the achievement of this important public health goal. Over the past decade, a large body of evidence has revealed convincing benefits of HPV vaccination in preventing cervical infections and precancers at the individual-level (i.e., direct effectiveness) as well as in reducing the population-level burden of disease (i.e., overall effectiveness). At this time, effectiveness of the vaccines on preventing cervical cancer is just beginning to emerge given that there is a prolonged latency period for invasive disease. As we enter the era of cervical cancer elimination, these early and promising results may be expected in other countries in the near future. Thus, monitoring the direct and overall effectiveness for cervical cancer is an urgent research priority. In this article, we summarize what is known about the effectiveness of HPV vaccines on precancerous outcomes, and we highlight considerations for continuing these important public health activities going forward to monitor progress toward cervical cancer elimination.

Elimination of cervical cancer in U.S. Hispanic populations: Puerto Rico as a case study

Cervical cancer remains a major burden for women around the world. In 2018, the World Health Organization called for the elimination of cervical cancer worldwide (<4 cases per 100,000 women-years), within the 21st century. In the U.S., despite great progress toward this goal, existing disparities among racial/ethnic groups in cervical cancer raise concerns about whether elimination can be achieved for all women. We describe: 1) disparities in cervical cancer among Hispanics in the U.S. and factors that contribute to their increased risk, 2) prevention and control efforts to increase equity in the elimination of cervical cancer in this population, and 3) cervical cancer control efforts in Puerto Rico (PR), a U.S. territory, as a case study for cervical cancer elimination among a minority and underserved Hispanic population. Hispanics have the highest incidence rates of cervical cancer among all racial/ethnic groups in the U.S. Despite being more likely to complete HPV vaccination series, lower cervical cancer screening and access to treatment may lead to a higher cervical cancer mortality in Hispanics compared to non-Hispanic White women. These disparities are influenced by multiple individual-, sociocultural-, and system-level factors. To achieve the goal of cervical cancer elimination in the U.S., systematic elimination plans that consider the needs of Hispanic populations should be included within the Comprehensive Cancer Control Plans of each state. Because PR has implemented coordinated efforts for the prevention and control of cervical cancer, it represents a notable case study for examining strategies that can lead to cervical cancer elimination among Hispanics.

National action towards a world free of cervical cancer for all women

Achieving equity in cervical cancer screening in low- and middle-income countries (LMICs): Strengthening health systems using a systems thinking approach

The World Health Organization (WHO) is leading a call to action to eliminate cervical cancer by the end of the century through global implementation of two effective evidence-based preventive interventions: HPV vaccination and cervical screening and management (CSM). Models estimate that without intervention, over the next 50 years 12.2 million new cases of cervical cancer will occur, nearly 60% of which are preventable only through CSM. Given that more than 80% of the cervical cancer occurs in low- and middle-income countries (LMICs), scaling up sustainable CSM programs in these countries is a top priority for achieving the global elimination goals. Multiple technologies have been developed and validated to meet this need. Now it is critical to identify strategies to implement these technologies into complex, adaptive health care delivery systems. As part of the coordinated cervical cancer elimination effort, we applied a systems thinking lens to reflect on our experiences with implementation of HPV-based CSM programs using the WHO health systems framework. While many common health system barriers were identified, the effectiveness of implementation strategies to address them was context dependent; often reflecting differences in stakeholder's belief in the quality of the evidence supporting a CSM algorithm, the appropriateness of the evidence and algorithm to context, and the 'implementability' of the algorithm under realistic assessments of resource availability and constraints. A structured planning process, with early and broad stakeholder engagement, will ensure that shared-decisions in CSM implementation are appropriately aligned with the culture, values, and resource realities of the setting.

Reducing cervical cancer deaths in women living with HIV: PEPFAR and the Go Further partnership

Women with HIV bear a significant burden of Human Papillomavirus (HPV) related cervical disease, and a have a higher risk of dying from cervical cancer should it occur. WLH have increased acquisition of HPV and decreased clearance, leading to persistent HPV infection: a risk for cervical cancer. The greatest burden of HIV in women occurs in sub-Saharan Africa where diagnostic and treatment services for cervical disease are limited. This paper will describe the epidemiology of HPV related cervical disease in women living with HIV (WLH) and the efforts to treat precursor lesions in HIV treatment programs supported by the President's Emergency Plan for AIDS Relief (PEPFAR.

Accelerating action on cervical screening in lower- and middle-income countries (LMICs) post COVID-19 era

Cervical cancer remains the fourth most common cancer in women, with 85% of deaths occurring in LMICs. Despite the existence of effective vaccine and screening tools, efforts to reduce the burden of cervical cancer must be considered in the context of the social structures within the health systems of LMICs. Compounding this existing challenge is the global COVID-19 pandemic, declared in March 2020. While it is too soon to tell how health systems priorities will change as a result of COVID-19 and its impact on the cervical cancer elimination agenda, there are opportunities to strengthen cervical screening by leveraging on several trends. Many LMICs maximized the strengths of their long established community-based primary care and public health systems with expansion of surveillance systems which incorporated mobile technologies. LMICs can harness the momentum of the measures taken against COVID-19 to consolidate the efforts against cervical cancer. Self-sampling, molecular human papillomavirus (HPV) testing and digital health will shift health systems towards stronger public health and primary care networks and away from expensive hospital-based care investments. While COVID-19 will change health systems priorities in LMICs in ways that may de-prioritize cervical cancer screening, there are significant opportunities for integration into longer-term trends towards universal health coverage, self-care and digital health.

Gaps between recommendations and their implementation: A register-based study of follow-up after abnormalities in cervical cancer screening

Follow-up after screen-detected abnormalities is crucial for the success of cervical cancer screening programs but is usually not closely monitored in official screening statistics. We determined how the follow-up deviated from the recommendations in the Danish organized program. Using Danish nationwide population-based registers, the follow-up pathways of 60,199 women aged 23-59 with non-negative screening samples from 2012 to 2014 were mapped until end of 2018. We studied the timeliness and appropriateness of follow-up tests after cervical cytology screening and the total resource use in accordance with the national recommendations. Regression analyses were used to determine variations in adherence according to age, provider type, region, and history of abnormalities. Among women referred for immediate colposcopy, 91.3% (95% CI: 90.9%-91.6%) attended within four months as recommended, whereas up to about half of the women with a recommendation for a repeat test received this test either too early or very late. Overall, only 43% (95% CI: 42.9%-43.7%) of women with non-negative screening tests received the recommended follow-up, whereas 18% (95% CI: 17.6%-18.2%) received more than was recommended, 35% (95% CI: 34.4%-35.1%) received some follow-up but less than recommended and 4% (95% CI: 3.9%-4.2%) were not followed up at all. These proportions varied by screening diagnosis, woman's age, type of health care provider, region, and history of abnormalities. On average, women underwent more tests of each type than recommended by the guidelines. Deviations from follow-up recommendations are very frequent even in organized cervical screening programs and should be routinely monitored by screening program statistics.

A lay health worker intervention to improve breast and cervical cancer screening among Latinas in El Paso, Texas: A randomized control trial

We examined the effectiveness of a lay health worker (promotora)-delivered intervention on increasing breast and cervical cancer screening among low-income, primarily uninsured Latinas living in El Paso, Texas. In 2015, Breast and Cervical Cancer Screening (BCCS) program promotoras recruited Latinas overdue for breast and/or cervical cancer screening in community settings. Promotoras consented eligible women and conducted baseline surveys before individually randomizing women into control (n = 313) or intervention (n = 314) groups. Control participants received printed material providing basic information about breast and cervical cancer screening.Intervention participants received promotora-delivered one-on-one breast and cervical cancer screening education followed by navigation calls, providing assistance to address personal and logistic barriers to accessing clinical services. We assessed breast and cervical cancer screening outcomes using a 6-month follow-up survey. Per protocol (PP) and intent to treat (ITT) analyses are reported. At follow-up, among women in need of breast cancer screening, those in the intervention group were significantly more likely to complete a mammogram than those in the control group (PP: 53.4% vs. 40.1%, p = .013; ITT: 47.9% vs. 35.2%, p = .011). Among women in need of Pap screening, only intervention group women 50 years and older were more likely to complete a Pap screening compared with control group women (PP: 64.5% vs. 43.5%, p = .019). A promotora-delivered behavioral intervention, embedded in a community-based organization, increased mammography uptake in all women and Pap uptake among women 50 years and older in a sample of low-income Latinas. NCT04397744.

Cervical cancer screening in the United States: Challenges and potential solutions for underscreened groups

Cervical cancer screening rates in the United States are generally high, yet certain groups demonstrate disparities in screening and surveillance. Individuals at greatest risk for cervical cancer are often from marginalized or underserved groups who do not participate in regular screening for a variety of reasons. Using the Population-based Research to Optimize the Screening Process (PROSPR) Trans-Organ Conceptual Model, including concepts of individual-, provider-, facility-, system-, or policy-level factors, we provide a commentary to highlight reasons for low screening participation among subgroups in the U.S. These include racial and ethnic minorities, rural residents, sexual and gender minorities, those with limited English proficiency, those with particular religious beliefs, and various health conditions. We describe barriers and offer potential solutions for each group. In addition, we discuss cross-cutting barriers to screening including difficulty interacting with the healthcare system (limited knowledge and health literacy, lack of provider recommendation/contact), financial (cost, lack of insurance), and logistical barriers (e.g., lack of usual source of care, competing demands, scheduling issues). Solutions to address these barriers are needed to improve screening rates across all underscreened groups. Changes at state and national policy levels are needed to address health insurance coverage. Mobile screening, ensuring that interpreters are available for all visits, and targeted in reach at non-gynecological visits can further overcome barriers. Employing community outreach workers can increase community demand for screening, and patient navigators can improve adherence to both screening and follow-up diagnostic evaluation. HPV self-sampling can address multiple barriers to cervical cancer screening.

A narrative review of HPV vaccination interventions in rural U.S. communities

Uptake of human papillomavirus (HPV) vaccine in the United States (U.S.) is far below the Healthy People 2020 goal of 80% coverage among adolescents. In rural communities, HPV vaccination coverage is low, yet incidence and mortality rates of HPV-associated cancer are high. Much of the research focused on HPV vaccination in rural U.S. communities has involved qualitative investigations, observations, survey research, and secondary data analysis with limited implementation of interventional study designs. The purpose of this narrative review was to examine intervention studies to increase HPV vaccination in rural settings and to summarize study characteristics and associated outcomes. PubMed, PsycINFO, CINAHL, and Web of Science were searched utilizing systematic narrative review methodology for studies describing implementation of HPV vaccination interventions in rural U.S. settings from January 2006-December 2019. Using specific search criteria, 991 studies were identified. After abstract review, 30 full-text articles were assessed for eligibility, and 15 met the inclusion criteria. The 15 articles - published from 2011 to 2019 - described HPV vaccination interventions in rural settings of six states, including communities, health clinics, and schools. A range of primary and secondary outcomes were reported, including HPV vaccine receipt (series initiation, continuation, and/or completion); HPV vaccine knowledge; and/or cervical cancer knowledge. Across the studies, there was an absence of the description of rural context. As compared to the broader HPV vaccination intervention literature, interventions in rural settings were limited. More interventional research is needed in rural communities given the elevated rates of HPV-related cancer and low rates of HPV vaccine uptake.

Equity enhancing policies that increase access and affordability of cervical cancer screening in the United States: A Preventive Medicine Golden Jubilee Commentary

A Golden Jubilee Editorial - Preventive Medicine's contributions to the science of cervical cancer elimination

Factors associated with timely colposcopy following an abnormal cervical cancer test result

Successful cervical cancer prevention requires screening and appropriate management of abnormal test results. Management includes diagnostic evaluation and treatment, if indicated, based on cervical cancer risk after most abnormal test results. There is little guidance on the optimal timing of diagnostic evaluation, and few data exist on factors associated with timely management. We quantified time-to-colposcopy within 12 months of an abnormal cervical cancer screening or surveillance test result from 2010 to 2018 across three diverse healthcare systems and described factors associated with timely colposcopy. Among 21-65 year-old patients with an abnormal test result for which colposcopy was indicated (n = 28,706), we calculated the proportion who received a colposcopy within 12 months of the abnormal test and used Kaplan-Meier methods to estimate the probability of colposcopy within 12 months. Across all systems, 75.3% of patients received a colposcopy within 12 months, with site-specific estimates ranging from 70.0 to 83.0%. We fit mixed-effects multivariable logistic regression models to identify factors associated with receipt of colposcopy within 12 months. The healthcare system and cytology result severity were the most important factors associated with of timely colposcopy. We observed that sites with more centralized processes had higher proportions of colposcopy completion, and patients with high-grade results were more consistently evaluated earlier than patients with low-grade results. Patient age also affected receipt of timely colposcopy, though this association differed by healthcare system and result severity. These data suggest opportunities for system-level interventions to improve management of abnormal cervical cancer test results.

Prevention, diagnosis and treatment of cervical cancer: A systematic review of the impact of COVID-19 on patient care

Worldwide, the COVID-19 pandemic disrupted healthcare services, including cervical cancer management, and an increased burden for this condition is expected. This systematic review synthetizes the available evidence on the impact of the pandemic on prevention, diagnosis and treatment of cervical cancer. Searches were performed on PubMed, Embase, and Scopus for relevant studies on these topics with the purpose of comparing service access and care delivery before and during COVID-19 pandemic. Due to the methodological heterogeneity among the studies, findings were narratively discussed. Of the 715 screened titles and abstracts, 33 articles were included, corresponding to 42 reports that covered the outcomes of interest: vaccination against human papillomavirus (HPV) (6 reports), cancer screening (19), diagnosis (8), and treatment (8). Seven studies observed reductions in HPV vaccination uptake and coverage during COVID-19. Reports on cervical screening and cancer diagnosis activities showed a substantial impact of the pandemic on access to screening services and diagnostic procedures. All but one study that investigated cervical cancer treatment reported changes in the number of women with cervical lesions who received treatments, as well as treatment delay and interruption. With a major impact during the first wave in 2020, COVID-19 and restriction measures resulted in a substantial disruption in cervical cancer prevention and management, with declines in screening and delays in treatment. Taken together, findings from this systematic review calls for urgent policy interventions for recovering cervical cancer prevention and care.

The effectiveness of health education interventions on cervical cancer prevention in Africa: A systematic review

Low levels of knowledge and awareness on cervical cancer play a role in limiting cervical cancer prevention uptake. This systematic review aimed to identify effective educational interventions to increase cervical cancer awareness, knowledge, and subsequently screening or vaccination uptake in African women. A literature search was conducted in Medline and EMBASE databases. We examined original, peer-reviewed English literature published between 2005 and 2020. Nineteen studies examining health education interventions' impact on awareness, knowledge, and screening or vaccination uptake in African women were included. Ten studies were controlled trials, nine performed pre- and post-measurements in one group. Most studies were published between 2015 and 2020 (86%), many were from Nigeria (47%). Studies were mostly set up in communities and schools. The most frequently used intervention was lectures, alone or combined with videos and practical demonstrations. Sixteen studies evaluated knowledge or awareness, and all showed a statistically significant improvement following the intervention. Of the ten studies that evaluated screening uptake, either as the single outcome or combined with knowledge or awareness, six found a significant rise in screening uptake after intervention. Educational interventions increased knowledge and awareness in African women, some boosted uptake of cervical cancer screening, especially when using peer health educators and culturally tailored methods. Innovative approaches such as self-collected HPV testing and mHealth also demonstrated a potential to increase uptake of screening. More research is needed to identify and analyse barriers to screening uptake, which can still be present even after a successful educational intervention.

A comparison of high-grade cervical abnormality risks in women living with and without human immunodeficiency virus undergoing routine cervical-cancer screening

As the US moves increasingly towards using human papillomavirus (HPV) testing with or without concurrent cytology for cervical cancer screening, it is unknown what the corresponding risks are following a screening result for women living with HIV (WLWH), which will dictate the optimal clinical follow-up. Therefore, using medical records data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in women aged 30-64 years in 2003, we compared risks of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe diagnoses (CIN2+) in women not known to have HIV (HIV[-] women) (n = 67,488) frequency matched 111:1 on age and year of the first co-test to the 608 WLWH (n = 608). WLWH were more likely to test HPV positive (20.2% vs. 6.5%, p < 0.001) and have non-normal cytology (14.1% vs. 4.1%, p < 0.001) than HIV[-] women. Five-year CIN2+ risks for all WLWH and HIV[-] women were 3.5% (95%CI = 2.0-5.0%) and 1.6% (95%CI = 1.5-1.8%) (p = 0.01), respectively. Five-year CIN2+ risks for WLWH with positive HPV and non-normal cytology, positive HPV and normal cytology, negative HPV and non-normal cytology, and negative HPV and normal cytology were 24.9% (95%CI = 13.4-36.4%), 3.0% (95%CI = 0.0-7.4%), 3.6 (95%CI = 0.0-9.8%) and 0.3% (95%CI = 0.0-0.8%), respectively. Corresponding 5-year CIN2+ risks for HIV[-] women were 26.6% (95%CI = 24.6-28.7%), 8.5% (95%CI = 7.2-9.9%), 1.9% (95%CI = 1.0-2.8%), and 0.5% (95%CI = 0.4-0.6%), respectively. Thus, in this healthcare setting, the main cause in overall CIN2+ risk differences between WLWH and HIV[-] women was the former was more likely to screen positive and once the screening result is known, it may be reasonable to manage both populations similarly.

Racial/ethnic inequalities in cervical cancer screening in the United States: An outcome reclassification to better inform interventions and benchmarks

In the United states (U.S.), prevailing understanding suggests significant racial/ethnic inequalities in cervical cancer screening exist. However, recent findings elsewhere in North America indicate the magnitude of these inequalities depend on the way screening is defined: lifetime screening versus up-to-date screening. As those who have never been screened are most at risk for invasive cancer, an improved understanding of inequalities in this outcome is necessary to better inform interventions. To describe racial/ethnic inequalities in 1) never screening and 2) not being up-to-date with screening among women who have been screened at least once in their lifetime, three years (2014-2016) of the U.S. Behavioral Risk Factor Surveillance Survey were utilized to estimate cervical cancer screening prevalence ratios via Poisson regression (N = 123,070). The sample was limited to women age 21 to 65 years. Women from racial/ethnic minority groups were more likely to never have been screened in comparison to White women, particularly women of Asian descent (Prevalence Ratio (PR) = 3.8, 95% CI = 3.3-4.3). However, among women who had been screened at least once in their lifetime, an inverse association was observed between being a member of a racial/ethnic minority group and not being up-to-date with screening (e.g. PR

Low rates of HPV vaccination and cervical cancer screening: Challenges and opportunities in the context of the COVID-19 pandemic

This invited commentary discusses the article by Richards et al. describing differences in rates of on-time HPV vaccination and cervical cancer screening in 2018 among enrollees in different insurance plans. The commentary focuses on the larger problem of low vaccination HPV rates and decreasing cervical cancer screening rates seen across all sectors. We outline challenges posed by the COVID-19 pandemic on HPV vaccination and cervical cancer screening, and discuss opportunities to improve cervical cancer prevention.

Women with obesity participate less in cervical cancer screening and are more likely to have unsatisfactory smears: Results from a nationwide Danish cohort study

Some studies found an association between obesity and increased cervical cancer risk, but potential mechanisms are unknown. In this nationwide register-based cohort study, we investigated the association between overweight/obesity and cervical cancer screening participation and risk of unsatisfactory smears. The study population was identified in the Danish Medical Birth Registry. We included 342,526 women aged 23-49 years with pre-pregnancy body mass index (BMI) registered during 2004-2013. Screening participation and unsatisfactory smears during up to four years after child birth were identified in a nationwide pathology register. We used absolute risk regression to estimate the relative absolute risk (RAR) with 95% confidence intervals (CIs) of screening participation according to BMI, adjusted for age, calendar year, sociodemographic characteristics, parity and previous high-grade cervical intraepithelial neoplasia. Among those who were screened (n = 295,482), we used log-binomial regression to investigate the relative risk (RR) of an unsatisfactory smear according to BMI, adjusted for age, year, parity, oral contraceptive use and pathology department. A lower proportion of obese women (79.3%) than women of normal weight (85.8%) were screened, and obese women had lower adjusted probability of being screened than women of normal weight (RAR

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.

Preventive care use among Hispanic adults with limited comfort speaking English: An analysis of the Medical Expenditure Panel Survey data

Language barriers have been associated with worse access to healthcare and poorer health outcomes. To assess differences in access to care and utilization of healthcare services between Hispanic adults and non-Hispanic white adults (NHW), we used the Medical Expenditure Panel Survey (2013-2016) to compare Hispanic adults who expressed limited comfort speaking in English (LCE) with Hispanic adults who were comfortable speaking in English (CE) and NHW adults. Hispanic adults with CE were less likely than NHW adults to have a usual source of care, use preventive services, including cervical cancer screening, and healthcare services. However, after adjustment breast and cervical cancer screening exceeded that of NHW adults. Hispanic adults with LCE fared substantially worse than their Hispanic counterparts with CE in having a usual source of care, use of preventive services, breast and colorectal cancer screening, and healthcare services. After adjustment, use of all cancer screening tests were similar. Eliminating disparities for Hispanic adults will require a multi-pronged approach to address access to healthcare and other social determinants of health, including poverty, employment discrimination, and educational inequities. The public health community can help improve health literacy, address barriers to care, and provide appropriate language assistance at point of care using culturally-competent means to promote greater utilization of preventive services, including demand for and delivery of cancer screenings.

HPV prevention and control – The way forward

The global confrontation with COVID-19 has not only diverted current healthcare resources to deal with the infection but has also resulted in increased resources in the areas of testing and screening, as well as educating most of the global public of the benefits of vaccination. When the COVID-19 pandemic eventually recedes, the opportunity must not be missed to ensure that these newly created resources are maintained and redeployed for use in testing and immunisation against other vaccine-preventable infectious diseases. A notable example is infection by human papillomavirus (HPV), the commonest sexually transmitted human virus and the leading cause of a variety of cancers in both men and women, such as cervical, head and neck, anal, vaginal, vulvar and penile cancers. The most important is cervical cancer, the objective of the global elimination goals targeting the vaccination of young female and male adolescents, screening all women and treatment of all infected women. As the campaigns to control SARS-CoV-2, the eradication of HPV-induced cancers also relies on effective prevention and control programs. The lessons learned and the technical, logistical and human resources which have been established to combat COVID-19 by vaccination and testing must be applied to the eradication of other infections which affect the global population. This commentary summarizes the opportunities that the COVID-19 pandemic has created for HPV prevention and control, lists the already available tools for HPV control, and emphasizes the potential public health threats amidst the ongoing COVID-19 pandemic.

Estimated projection of cancer mortality in Taiwan until 2050

Childhood body fatness and the risk of epithelial ovarian cancer: A population-based case-control study in Montreal, Canada

To assess the association between childhood body fatness and epithelial ovarian cancer (EOC), and whether this association differs by type of EOC. Using data from a population-based case-control study (497 cases and 902 controls) in Montreal, Canada conducted 2011-2016, we examined the association between childhood body fatness and EOC, overall and separately for invasive vs. borderline EOCs. A figure rating scale was used to measure body fatness at ages 5 and 10. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Quantitative bias analyses were conducted to assess the impact of exposure misclassification and non-participation. The aOR (95% CI) of overall EOC for high vs. low body fatness was 1.07 (0.85-1.34) at age 5 and 1.28 (0.98-1.68) at age 10. The associations were stronger for invasive EOC, specifically the endometrioid histological type. For borderline cancers, the aORs were below the null value with wide confidence intervals. Bias analyses did not reveal a strong influence of non-participation. Non-differential exposure misclassification may have biased aORs towards the null for invasive cancers but did not appear to have an appreciable influence on the aORs for borderline cancers. Childhood body fatness may be a risk factor for invasive EOC in later adult life. Our study highlights the potential importance of examining early life factors for a comprehensive understanding of EOC development.

What rate of Iranian women perform Pap smear test? Results from a meta-analysis

In this study, an attempt was made to estimate the aggregated proportion of Pap smear test uptake among women in Iran from 2012 to 2022 using meta-analysis. The data collection process involved reviewing records registered in databases between January 1, 2012, and September 11, 2022. The final data was analyzed using random effects models, and potential heterogeneity was assessed using the I2 index. To examine publication bias, Egger's test and Funnel Plot were employed. Sensitivity analysis, specifically single study exclusion Meta-analysis, was conducted to assess the influence of each individual study on the aggregated percentage of Pap smear test uptake. A total of 28,754 women were included across the 33 articles analyzed. The pooled percentage of Pap smear test uptake for both one-time and regular screenings was found to be 46.52% (95% CI: 40.91 to 52.14) and 17.80% (95% CI: 12.42 to 23.18), respectively. No significant evidence of publication bias was detected, although the influence of smaller studies was confirmed. Sensitivity analysis indicated that the overall rate of Pap smear test uptake was not highly sensitive to the results of individual studies. The findings emphasize the low rate of regular Pap smear testing among Iranian women and suggest that tailored interventions considering cultural and geographical factors specific to different provinces in Iran could help increase the utilization of this screening service.

Interventions using mHealth strategies to improve screening rates of cervical cancer: A scoping review

MHealth interventions are extensively used to inform and remind women about cervical cancer and their upcoming screening appointments. Our scoping review aims to examine the effectiveness these interventions targeted to increase the uptake of cervical cancer screening along with its barriers and facilitators. We searched 4 databases (PsycINFO. PUBMED, CINAHL, and MEDLINE) for studies that were published between January 1, 2009 and October 2019. References were further screened manually for additional papers. Studies were included in the review if they used interventions including phone calls, text messages and mobile applications as their primary strategy to contact women. We identified 12 unique studies that met the inclusion criteria; seven were international studies. Most studies sent multiple messages (informative and reminder) and/or made numerous phone calls (manual/automated) to inform participants about cervical cancer screening, their nearest screening clinic, and their upcoming appointments. Five studies documented a significant increase in the uptake of cervical cancer screenings during the follow-ups conducted within 12 months. Qualitative studies suggested participants prefer particular communication mediums, and they were concerned about privacy and confidentiality issues when text messages were sent with their health information. Findings suggest mHealth interventions may be an effective strategy to reach women for improving their cervical cancer uptake. Barriers including transportation cost, inaccessibility, and inability to come for walk-in appointments in the health clinics need to be addressed, beyond reminders, in mobile phone-based interventions to facilitate their presence in their next appointment.

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.

Recent changes in cervical cancer screening guidelines: U.S. women's willingness for HPV testing instead of Pap testing

Cervical cancer screening guidelines in the United States were revised in 2018 to include the option of primary human papillomavirus (HPV) testing. The transition to this screening method may face difficulties as Pap testing has been the primary screening modality in the United States. The objective of this study is to assess information, motivation, and behavioral skills associated with willingness to receive an HPV test instead of a Pap test among women. The sample included U.S. 812 women, ages 30 to 65 years. Participants completed an online survey in 2018. The Information, Motivation, and Behavioral Skills (IMB) model was used to measure predictors of willingness for HPV testing. The outcome variables were willingness to receive the HPV test instead of the Pap test, with and without time interval details. Logistic regression modeling was used with SAS 9.4. Over half of the sample (55%) were willing to receive the HPV test. For the information domain, HPV knowledge was significantly associated with willingness for HPV testing (OR = 1.08, 95%CI 1.04-1.13). Significant motivating factors included: positive attitudes, social norms, perceived benefits, worry about cervical cancer, and worry about abnormal HPV tests. For behavioral skills, women were significantly more willing to get the HPV test if a provider recommended it (OR = 2.43, 95%CI 1.53-3.87) and currently up-to-date on cervical cancer screening guidelines (OR = 1.52, 95%CI 1.52-2.26). Addressing barriers and facilitators to willingness to transition to primary HPV testing over Pap testing is needed as the United States has updated guidelines for cervical cancer screening.

Variation in the receipt of human papilloma virus co-testing for cervical screening: Individual, provider, facility and healthcare system characteristics

Since 2012, cervical cancer screening guidelines allow for choice of screening test for women age 30-65 years (i.e., Pap every 3 years or Pap with human papillomavirus co-testing every 5 years). Intended to give patients and providers options, this flexibility reflects a trend in the growing complexity of screening guidelines. Our objective was to characterize variation in cervical screening at the individual, provider, clinic/facility, and healthcare system levels. The analysis included 296,924 individuals receiving screening from 3626 providers at 136 clinics/facilities in three healthcare systems, 2010 to 2017. Main outcome was receipt of co-testing vs. Pap alone. Co-testing was more common in one healthcare system before the 2012 guidelines (adjusted odds ratio (AOR) of co-testing at the other systems relative to this system 0.00 and 0.50) but was increasingly implemented over time in a second with declining uptake in the third (2017: AORs shifted to 7.32 and 0.01). Despite system-level differences, there was greater heterogeneity in receipt of co-testing associated with providers than clinics/facilities. In the three healthcare systems, providers in the highest quartile of co-testing use had an 8.35, 8.81, and 25.05-times greater odds of providing a co-test to women with the same characteristics relative to the lowest quartile. Similarly, clinics/ facilities in the highest quartile of co-testing use had a 4.20, 3.14, and 6.56-times greater odds of providing a co-test relative to the lowest quartile. Variation in screening test use is associated with health system, provider, and clinic/facility levels even after accounting for patient characteristics.

A world without cervical cancer is within our reach

Human papilloma virus vaccination and cervical cancer screening coverage in managed care plans — United States, 2018

Human papilloma virus (HPV) vaccination for adolescents aged 11-12 years and cervical cancer screening for women aged 21-65 years are recommended to help prevent cervical cancer. The purpose of this study was to describe 2018 National Committee for Quality Assurance (NCQA) Healthcare Effectiveness Data and Information Set (HEDIS®) data for the United States on HPV vaccination and cervical cancer screening from 275 commercial preferred provider organizations (PPOs), 219 commercial health maintenance organizations (HMOs), and 204 Medicaid HMOs. The Centers for Disease Control and Prevention and NCQA analyzed the data in 2021. The HEDIS® measure for HPV vaccination was the percentage of male and female adolescents aged 13 years who completed HPV immunization (2- or 3-dose series) on or before their 13th birthday. The measure for cervical cancer screening was the percentage of women screened either with cervical cytology within the last 3 years for women aged 21-64 years or with cervical cytology/HPV co-testing within the last 5 years for women aged 30-64 years. Nationally, the mean rate for HPV vaccination in 2018 was 37.8% in Medicaid HMOs, 30.3% in commercial HMOs, and 24.9% in commercial PPOs. The mean rate for cervical cancer screening was 75.9% in commercial HMOs, 72.6% in commercial PPOs, and 60.3% among Medicaid HMOs. Medicaid HMOs reported higher HPV vaccination rates but lower cervical cancer screening rates than commercial plans. These differences raise questions about explanatory factors and how to improve prevention performance by plan category.

Cancer mortality among solid organ transplant recipients: A systematic review and meta-analysis

Cognitions and behaviours of general practitioners in France regarding HPV vaccination: A theory-based systematic review

Human papillomavirus (HPV) vaccination is safe and efficacious to prevent persistent HPV infection, precancerous anogenital lesions and cervical cancer. However, in countries where vaccination programmes are implemented outside of schools, such as France, reaching high HPV vaccination coverage of the target population is challenging. Many studies have been performed in France to assess cognitions of general practitioners (GPs) regarding HPV vaccination. However, the evidence is not consistent about which cognitions are key. To provide a comprehensive overview, we performed a systematic review of studies conducted in France on GPs' cognitions regarding HPV vaccination and used the reasoned action approach to extract and synthesize data. The systematic search was performed up to July 2020 in Medline via PubMed, PsycINFO, PsycARTICLES, Embase, CINAHL Plus, Web of Science, Pascal and Francis databases. Grey literature was searched for in the French Public Health Database, Cairn. Info, yahoo.fr, and Google Scholar. Twenty-five scientific publications were selected based on eligibility criteria and assessed for quality. Our qualitative synthesis highlights that although 73% of GPs report recommending HPV vaccination, up to 50% would not recommend it because of concerns, including changes in patients' health behaviours and doubts about safety and/or efficacy. GPs' injunctive norms, i.e. trust in institutional information, were shown to be associated positively with GPs' willingness to recommend HPV vaccination. Parents' fears, girls' age, and potential connection with sexuality do not seem to affect GPs' recommendations. These results will inform the development of a professional educational intervention targeting GPs in France.

Differences in cervical test coverage by age, socioeconomic status, ethnic origin and municipality type – A nationwide register-based study

An invitational organized cervical cancer screening together with widely spread opportunistic testing has coexisted for decades in Finland. The aim of this study was to examine the coverage of cervical tests by age, socioeconomic status, ethnicity and municipality type within and outside the organized screening program. We had a cohort of women of whom 1,2 million were in the target age range of screening and residing in Finland in 2010-2014. Data on Pap and/or HPV -tests within and outside the screening program were collected from the Mass Screening Registry, the pathology laboratories and the health insurance reimbursement registry and five-year population coverages of tests were reported. The total test coverage was 86.0%; 95% CI, (85.8-86.1), and was notably lower for those with an unknown socioeconomic status and pensioners (68.8%; 95% CI, (67.9-69.6) and 77.1%; 95% CI, (76.5-77.6), respectively) compared to upper-level employers (89.8%; 95% CI, (89.5-90.2)). Coverage was also lower for non-native speaking women (72.4%; 95% CI, (71.8-73.0)) compared to native speakers (86.9%; 95% CI, (86.7-87.0)) and for women living in urban municipalities (85.5%; 95% CI, (85.3-85.7)) compared to semi-urban (87.4%; 95% CI, (87.0-87.8)). Although overall coverage was high, tests within and outside the program seemed to concentrate on women with presumably good access to health services. Tests outside the program were especially common among young women who are at a low risk of invasive cervical cancer. Efforts should be made to reduce excessive opportunistic testing and to increase attendance at the program among hard-to-reach populations.

Impact of screening between the ages of 60 and 64 on cumulative rates of cervical cancer to age 84y by screening history at ages 50 to 59: A population-based case-control study

There is little empirical data on the absolute benefit of cervical screening between ages 60-64y on subsequent cancer risk. We estimate the incidence of cervical cancer up to age 84y in women with and without a cervical cytology test at age 60-64y, by screening histories aged 50-59y. The current study is a population based case-control study of women born between 1928 and 1956 and aged 60-84y between 2007 and 2018. We included all such women diagnosed with cervical cancer in England and an aged-matched random sample without cancer. Women with a hysterectomy were excluded. Exposure was cervical cytology between ages 50-64y. The main outcome was 25y cumulative risk of cervical cancer between ages 60-84y. We found that eight in every 1000 (8.40, 95%CI: 7.78 to 9.07) women without a screening test between age 50-64y develop cervical cancer between the ages of 60-84y. The risk is half: 3.46 per 1000 (95%CI: 2.75 to 4.36) among women with a test between age 60-64y but no cervical screening test at age 50-59y. The absolute difference in risk is equivalent to one fewer cancer for every 202 such women screened. The highest risk (10.01, 95%CI:6.70 to 14.95) was among women with abnormal screening at ages 50-59y and no tests 60-64y. 25y risk among women with a screening test every five years between age 50-64y was just under two in a 1000 (1.59, 95%CI:1.42 to 1.78). Results suggest the upper age of screening should be dependent on previous screening participation and results.

Introduction of HPV testing for cervical cancer screening in Central America: The Scale-Up project

The Scale-Up project introduced vaginal self-sampling and low-cost human papillomavirus (HPV) testing as the primary approach for cervical cancer screening in selected public health centers in Guatemala, Honduras, and Nicaragua. We evaluate the country-specific accomplishments in screening: target-coverage, triage, and treatment. Between 2015 and 2018, cervical cancer screening was offered to women at least 30 years of age. Triage of HPV-positive women was based on visual inspection with acetic acid or Pap. Aggregated data included total women screened, use of self-sampling, age, time elapsed since last screening, HPV results, triage tests, triage results, and treatment. A total of 231,741 women were screened for HPV, representing 85.8% of the target populations within the project. HPV positivity was lower in Guatemala (12.4%) compared to Honduras and Nicaragua (14.5% and 14.2%, respectively, p < 0.05). A follow-up triage test was completed for 84.2%, 85.8%, and 50.1% of HPV-positive women in Guatemala, Nicaragua, and Honduras, respectively. Of those with a positive triage test, 84.7%, 67.1%, and 58.8% were treated in Guatemala, Nicaragua, and Honduras, respectively. First-time screening was highest in Nicaragua (55.8%) where self-sampling was also widely used (97.1%). The Scale-Up project demonstrated that large-scale cervical cancer screening and treatment intervention in a high-burden, low-resource setting can be achieved. Self-sampling and ablative treatment were key to the project's achievements. Data monitoring, loss to follow-up, and triage methods of screen- positive women remain critical to full success.

The value of adding a single co-test in HPV primary screening

The screening program for cervical cancer in Sweden, recommends screening with HPV test primarily for women over 30 years, but at the first screening test that is performed after the age of 40, both HPV test and cytology is recommended, so-called co-testing. The aim of this study was to examine how many cases of HPV negative cervical dysplasia that were found in this age-group, to be able to estimate the value of adding a co-test in an HPV screening program. A retrospective study of all abnormal cytological samples found in the cytology based screening program in the age group 41-45 years during the years 2012-2016 in the Region of Örebro County was performed. Out of the 10,511 women included in the study, 468 had an abnormal cytology screening test and 255/468 were HPV negative. The vast majority of the HPV negative cases had a normal cytology test as first follow-up. Of cases with remaining cytological abnormality, only four cases had histologically confirmed high-grade cervical dysplasia (CIN2) and no cases of HPV negative adenocarcinoma in situ or invasive cancer were found. Conclusion: With adding a single co-test to a HPV-based screening program, only a few extra cases of high-grade cervical dysplasia were found and the clinical significance of these cases is unclear.

Worldwide use of HPV self-sampling for cervical cancer screening

An increasing body of evidence supports the validity of self-sampling as an alternative to clinician collection for primary Human Papillomavirus (HPV) screening. Self-sampling effectively reaches underscreened women and can be a powerful strategy in low- and high-resource settings for all target ages. This work aims to summarize the current use of HPV self-sampling worldwide. It is part of a larger project that describes cervical cancer screening programmes and produces standardized coverage estimates worldwide. A systematic review of the literature and official documents supplemented with a formal World Health Organisation country consultation was conducted. Findings show that the global use of HPV self-sampling is still limited. Only 17 (12%) of countries with identified screening programs recommend its use, nine as the primary collection method, and eight to reach underscreened populations. We identified 10 pilots evaluating the switch to self-sampling in well-established screening programs. The global use of self-sampling is likely to increase in the coming years. COVID-19's pandemic has prompted efforts to accelerate HPV self-sampling introduction globally, and it is now considered a key element in scaling up screening coverage. The information generated by the early experiences can be beneficial for decision-making in both new and existing programs.

Implementation research to accelerate scale-up of national screen and treat strategies towards the elimination of cervical cancer

Cervical cancer is a significant public health problem, with 570,000 new cases and 300,000 deaths of women per year globally, mostly in low- and middle-income countries. In 2018 the WHO Director General made a call to action for the elimination of cervical cancer as a public health problem. New thinking on programmatic approaches to introduce emerging technologies and screening and treatment interventions of cervical precancer at scale is needed to achieve elimination goals. Implementation research (IR) is an important yet underused tool for facilitating scale-up of evidence-based screening and treatment interventions, as most research has focused on developing and evaluating new interventions. It is time for countries to define their specific IR needs to understand acceptability, feasibility, and cost-effectiveness of interventions as to design and ensure effective implementation, scale-up, and sustainability of evidence-based screening and treatment interventions. WHO convened an expert advisory group to identify priority IR questions for HPV-based screening and treatment interventions in population-based programmes. Several international organizations are supporting large scale introduction of screen-and-treat approaches in many countries, providing ideal platforms to evaluate different approaches and strategies in diverse national contexts. For reducing cervical cancer incidence and mortality, the readiness of health systems, the reach and effectiveness of new technologies and algorithms for increasing screening and treatment coverage, and the factors that support sustainability of these programmes need to be better understood. Answering these key IR questions could provide actionable guidance for countries seeking to implement the WHO Global Strategy towards cervical cancer elimination.

Risk-stratified screening and colorectal cancer incidence and mortality: A retrospective study from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Population-based cervical screening with Human Papillomavirus self-sampling at home and incidence of cervical cancer in Sweden

To describe the Swedish 2020 switch to primary cervical screening using Human Papillomavirus (HPV) self-sampling at home and compare with cervical cancer incidence trends. Statistics on HPV self-sampling and cervical cancer incidence up to 2024-12-31 were obtained from comprehensive nationwide registries. HPV self-sampling was recommended in 2017 for non-attending women and was in 2020 recommended as a primary screening for all women aged 23-70 years of age. During 2016-2020 there were  200,000 self-samples are taken annually (about half of all screening tests). During 2015 to 2020 the cervical cancer incidence was stable, between 11 and 12 per 100,000 women. From 2021 and onwards the incidence is declining and was 7,7/100,000 in 2024. The decline is stronger among women younger than 30 (-60%) but is strong in all ages (-27%). A rapid introduction of primary HPV self-sampling at home in 2020-2021 was followed by a rapid decline in invasive cervical cancer incidence.

Barriers to and facilitators of cancer prevention services for transgender and gender-diverse people: A systematic review

Despite the increasing adoption of gender-inclusive policies, transgender and gender-diverse (TGD) people continue to face significant barriers to cancer prevention services, resulting in low uptake of cancer screening and HPV vaccination. This review aimed to synthesize evidence on barriers and facilitators to cancer prevention among TGD people to inform more inclusive and effective policies and programmes. Searches were performed in Medline (1946), Cochrane CENTRAL (1992), CINAHL (1982), PsycINFO (1806), Web of Science (1975), and EMBASE (1971) from inception up to July 18, 2025. Thematic synthesis was guided by SURE framework, and McLeroy's socioecological model of health behaviour, adapted to cancer prevention context. A total of 1648 records were retrieved; 119 full texts were assessed and 53 studies (55 reports) met inclusion criteria. Most studies addressed cervical cancer and HPV-related prevention. Barriers were identified at individual (knowledge gaps, gender dysphoria, financial precarity), interpersonal (misgendering, discrimination, inadequate communication), healthcare-system (gendered services, insurance mismatches, lack of provider training), and societal levels (gendered messaging, stigma). Facilitators across the same levels included informed provider recommendations, affirming care environments and self-administered screening. Findings show that TGD people continue to experience exclusion within cancer prevention services. Addressing these disparities requires coordinated action across individual, interpersonal, system and societal levels.

Is elimination of cervical cancer in sight in England?

The age-standardised rate of cervical cancer is 8.5 per 100,000 in England, double the WHO "elimination" goal of 4.0 per 100,000, despite England being close to the target coverage for both HPV vaccination and cervical screening. Our aim was to see whether trends in mortality and incidence rates suggest that England is on the path to elimination. We discuss trends in mortality since 1953 by birth cohort, and cancer and cancer-in-situ incidence since 2000 by age group in relation to screening and vaccination. Mortality trends suggest a steep decline in HPV prevalence from women born in the 1880s to those born in the 1930s followed by a continuing increase. Cancer incidence and mortality then fell steeply after the introduction of national screening in 1988. Since 2004 women were invited for their first screen at age 25. From 2000-2004 to 2010-2014 invasive cancer incidence at age 25-29 doubled and mortality increased by 77 %. From 2015 to 2022 cervical cancer incidence fell by 90 % below age 25 and by 80 % at age 25-29 following the introduction of HPV vaccination for girls born since 1991. Raising the age of starting screening from 20 to 25 transiently increased incidence and mortality in women born 1984-1990. Vaccination may enable the NHS to reach its target for cervical cancer incidence of 4.0 per 100,000 by 2040. Whether the switch from cytology to primary HPV testing in 2019 will reduce rates among unvaccinated women born before 1991 is not yet clear.

Travel distance to the general practitioner and women's participation in cervical cancer screening in Denmark – A population-based cohort study, 2017

Previous studies found disparities in utilization of cervical cancer screening programs. Geographical distance to the screening location may affect women's participation. The aim of this study was to investigate the association between travel distance from residence to general practitioner, and invited women's participation in a national screening program for cervical cancer. Data were obtained from Danish national registers including all women invited to the screening program in 2017 (n = 341,708). Travel distance from residence to the general practitioner was calculated based on geocoded addresses and the road network. Multilevel logistic regression was used to calculate odds ratios (ORs) of participation with 95 % confidence intervals (CI). Based on 271,959 women with complete information, screening participation decreased from 67.7 % among women with a travel distance of 1.0-4.9 km to 61.1 % among women with ≥15.0 km. Adjusted for ethnicity, education, and age, women with ≥15.0 km to the general practitioner had 22 % lower odds of participation compared to those living 1.0-4.9 km away (OR = 0.78, 95 %CI [0.75;0.81]). Women with <1.0 km to the general practitioner had 10 % lower odds of participation (OR = 0.90, 95 %CI [0.88;0.93]). Sensitivity analysis indicated an exposure-response relationship when distance was ≥5 km, implying lower odds of participation with increasing distance above 5 km. Travel distance to the general practitioner was associated with participation in screening. Future initiatives should promote equal access to preventive health services focusing on women having a long travel distance to their general practitioner, as well as those living very close to their general practitioner.

Emotional barriers pose the greatest threat to cervical cancer screening for young adult women in the United Kingdom

Low cervical screening coverage rate is the root-cause of cervical cancer mortality in the United Kingdom (UK), with 99 % of deaths being considered preventable. Research has consistently categorised reasons for non-attendance into emotional, practical, and cognitive barriers. Despite this, public health interventions have been unable to improve coverage rates. We propose a lifespan perspective is needed, to enable targeted interventions at appropriate milestones (i.e., common life events) during a woman's life. We start this lifespan perspective by investigating the perceived barriers young women report, who have and have not yet been invited to their first cervical screen (i.e., a common life event). Twenty-nine women not yet invited to their first cervical screen and twenty women who confirmed they received their invite and confirmed attendance status, rated the likelihood of emotional, practical, and cognitive barriers affecting their attendance at their next cervical screen. Data collected between January and April 2018. Women who did not attend their first screen, rated emotional barriers significantly higher than all groups, and cognitive barriers higher than those women who did attend. Results highlight, for the first time, that commonly reported barriers are present up to seven years prior to a woman's first eligible cervical screen, with emotional barriers rated most strongly. Emotional barriers pose the greatest threat to cervical screening attendance in young adult women. Interventions should start at school to encourage cervical screening to be viewed as routine healthcare. Future research should continue a lifespan perspective, indexed to common life events.

Determining the optimal cervical cancer screening exit strategy in the Netherlands

In the Netherlands, women are currently invited for human papillomavirus (HPV) screening until age 60 (or age 65 for HPV-positive women). New data from HPV screening implementation in the Netherlands improved understanding of its longer-term protective effects and risk differences between population subgroups. With this, our aim was to optimize screening exit strategies. The microsimulation model MISCAN-Cervix was used to simulate a population of unvaccinated women born between 1962 and 1992 over their lifetime. We simulated 20 different exit strategies, varying by screening end ages and screening interval dependent on previous HPV status, with two triage methods (cytology triage or direct colposcopy referral for HPV16/18+ women aged ≥60). Main outcome measures were total and unnecessary colposcopy referrals (i.e. ≤ cervical intra-epithelial neoplasia stage 1), cancer cases and deaths prevented, and (quality-adjusted) life years gained ((QA)LYG). The incremental cost-effectiveness ratios (ICERs) were calculated for scenarios on the cost-effectiveness frontier. Screening of HPV-positive women at age 65 and age 70, with direct colposcopy referral of HPV16/18+ women aged ≥60 was the optimal exit strategy considering a threshold of €50,000 per LYG (ICER: €20,190/LYG, €46,985/QALY). This resulted in 18 additional cancer deaths prevented and 158 additional unnecessary referrals per 100,000 simulated women compared to the current strategy. Direct colposcopy referral of HPV16/18+ women aged ≥60 improved cost-effectiveness in all scenarios. In the Dutch HPV screening program, adding screening moments for older HPV-positive women and/or incorporating direct referrals for HPV16/18+ women is cost-effective and could increase the efficiency and effectiveness of screening.

Organized cervical cancer screening: A randomized controlled trial assessing the effect of sending invitation letters

To evaluate the effect of implementing two modalities of organized Cervical Cancer Screening (CCS) program on screening uptake after a six-month delay. A three-armed cluster randomized control trial was conducted in France between January 8 and July 2, 2021, involving148 510 women aged 40 to 65 and 1070 general practitioners. In the Optimized screening group, an invitation letter was posted to non-adherent women, and general practitioners were sent a list of their non-adherent patients. In the Organized screening group, an invitation letter was posted to non-adherent women. In the Usual care group, no invitation was sent. The endpoint was cervical cancer screening uptake after a six months period a) among all eligible women (primary endpoint); and b) among initially non-adherent women (post-hoc analysis). Statistical analysis was based on a logistic mixed model that compared between-group percentages of adherent women. A hierarchical comparison successively tested differences between the three arms (alpha 5 % risk). Among all 148,510 eligible women, screening uptake was 63.6 % (31,731/49910) in the Optimized screening group vs 61.8 % (30,210/48847) in the Usual care group (OR [IC95 %] = 1.05[0.93; 1.18]). Among the 64,370 initially non-adherent women, screening uptake was 17.9 % (3955/22134) in the Optimized screening group vs 11.6 % (5321/20995) in the Usual care group (OR [IC95 %] = 1.70[1.56;1.86]). There was no significant difference between Optimized and Organized screening groups (17.2 % vs 17.9 %; OR [IC95 %] = 1.02[0.94; 1.11]). The implementation of an organized screening based on an invitation letter resulted in a modest increase in participation among non-adherent women six months later.

Lower incidence of vaginal cancer after cervical human papillomavirus screening - long-term follow-up of Finnish randomized screening trial

Around 70% of vaginal cancers and 40-50% of vulvar cancers are attributable to human papillomavirus (HPV). Globally the burden of these diseases is estimated to grow due to the increasing HPV prevalence and rapidly aging global population. We aimed to examine if HPV screening for cervical cancer has an additional beneficial effect in preventing vaginal and vulvar cancers. To assess this, we used long-term follow-up data from the Finnish randomized HPV screening trial. Between 2003 and 2008, over 236,000 women were individually randomized (1:1) to primary HPV or cytology screening in Southern Finland. We followed this cohort up to the year 2020. To compare the study arms, we calculated site-specific and pooled incidence rate ratios (IRRs) and mortality rate ratios (MRRs) for vaginal and vulvar cancers using Poisson regression. During 3,5 million person-years of follow-up, the IRR for vaginal cancer in the HPV arm compared to the cytology arm was 0.40 (95% CI 0.17-0.88) and the corresponding MRR was 0.74 (95% 0.21-2.24). The corresponding IRR for vulvar cancer was 0.73 (95% 0.50-1.08) and the MRR was 0.64 (95% 0.23-1.62). The pooled IRR was 0.67 (95% 0.47 ̶ 0.95) and MRR 0.67 (95% 0.31 ̶ 1.37). We found lower incidence of vaginal cancers with HPV screening compared to cytology screening. To validate our results, we recommend analyzing data on vaginal and vulvar cancers also from other HPV screening studies.

Cervical cancer screening activity in the Capital Region of Denmark before, during and after the COVID-19 pandemic

Denmark went through various COVID-19 pandemic restrictions including periodic lockdowns from March 2020 to January 2022. All cancer screening programs were kept operational, yet access to clinicians for cervical screening was at times limited. We assessed the impact of the pandemic on cervical cancer screening activity in the Capital Region of Denmark. Cervical screening activity was defined as regular screening by invitation, opportunistic screening, and screening participation by HPV self-sampling. Activity was monitored during and post-pandemic and compared relatively to a 3-year pre-pandemic reference. The activity of cervical cancer screening was initially affected by the pandemic lockdowns, but increased activity during summer 2020 partly compensated this effect. Regular screening activity decreased 8.4% in 2020 and returned to pre-pandemic levels in 2021. During 2022 restrictions were removed and the decrease in activity was recorded to be 2.3%. Opportunistic screening activity was reduced by 14.3% in 2020 and 12.6% in 2021. A continued post-pandemic opportunistic screening activity reduction of 18.5% was observed, possibly related to changed patterns of primary health care use introduced during the pandemic. Screening by HPV self-sampling increased from 17.1% in the pre-pandemic period to 21.2% during the pandemic. Significantly more acceptance was recorded amongst older women (p < 0.0001). This increase mirrors the decrease in total clinician collected sample activity during the pandemic, where an increased reduction by age was observed. Post-pandemic HPV self-sampling participation decreased to 12.8%, possible reflecting a temporarily changed composition and motivation in the group of women invited for self-sampling.

Squamocolumnar junction visibility, age, and implications for cervical cancer screening programs

Visual assessment is currently used for primary screening or triage of screen-positive individuals in cervical cancer screening programs. Most guidelines recommend screening and triage up to at least age 65 years old. We examined cervical images from participants in three National Cancer Institute funded cervical cancer screening studies: ALTS (2864 participants recruited between 1996 to 1998) in the United States (US), NHS (7548 in 1993) in Costa Rica, and the Biopsy study (684 between 2009 to 2012) in the US. Specifically, we assessed the visibility of the squamocolumnar junction (SCJ), which is the susceptible zone for precancer/cancer by age, as reported by colposcopist reviewers either at examination or review of cervical images. The visibility of the SCJ declined substantially with age: by the late 40s the majority of people screened had at most partially visible SCJ. On longitudinal analysis, the change in SCJ visibility from visible to not visible was largest for participants from ages 40-44 in ALTS and 50-54 in NHS. Of note, in the Biopsy study, the live colposcopic exam resulted in significantly higher SCJ visibility as compared to review of static images (Weighted kappa 0.27 (95% Confidence Interval: 0.21, 0.33), Asymmetry chi-square P-value<0.001). Lack of SCJ visibility leads to increased difficulty in diagnosis and management of cervical precancers. Therefore, cervical cancer screening programs reliant on visual assessment might consider lowering the upper age limit for screening if there are not adequately trained personnel and equipment to evaluate and manage participants with inadequately visible SCJ.

HPV self-sampling among cervical cancer screening users in Spain: A randomized clinical trial of on-site training to increase the acceptability

A randomized clinical trial was conducted to compare the impact of two different instructions on vaginal self-sampling in its acceptability and willingness for future screening rounds among women attending cervical cancer screening (CCS). From November 2018 to May 2021, women aged 30-65 living in Spain attending CCS were randomized 1:1 in two arms. In the "On-site training arm (TRA)", women took a self-sample at the primary health care centre following provider's instructions. In the "No on-site training arm (NO-TRA)" women only received instructions to take self-sample at home. All women had to return a new sample collected at home one month after the baseline visit and an acceptability questionnaire. The proportion of self-samples returned, and acceptability was computed by the study arm. A total of 1158 women underwent randomization, 579 women per arm. At follow-up, women in TRA were more likely to return the home sample than women in the NO-TRA (82.4% and 75.5% respectively; p = 0.005). Over 87% of all participants favoured home-based self-sampling approach for future CCS, similar by arm. Over 80% of women in both arms chose to collect and return the self-sample at a health centre or pharmacy. Home-based self-sampling was a highly accepted strategy for CCS in Spain. Trying it first with prior on-site training at the health centre significantly increased the sample's return suggesting that a provider's supervision raised confidence and adherence. It is an option to consider when moving to self-sampling in established CCS. Preferred delivery sites most likely contextual. Registration on ClinicalTrials.gov: NCT05314907.

Do age-based discontinuation recommendations influence cervical cancer screening rates? Evidence from the United States' Behavioral Risk Factor Surveillance System, 2016 and 2018

The United States Preventive Services Task Force (USPSTF) recommends that women with adequate prior screening and average cervical cancer risk discontinue routine cervical cancer screening after age 65. This study's objective was to estimate how the USPSTF recommendation affects Papanicolaou (Pap) test rates among women at age 66 in the United States. We used nationally representative 2016 and 2018 Behavioral Risk Factor Surveillance System data for women ages 56-76 (n = 226,031) and a regression discontinuity design to estimate changes in annual Pap test rates at age 66. Among women age 66-76, 22.5% reported receiving a Pap test within the past one year. At age 66, annual Pap rates declined by 5.9 percentage points (p.p.) (95% Confidence Interval [CI]: -7.7, -4.1) off a pre-66 rate of 39%. The change varied by race/ethnicity, education, and marital status. Pap rates did not change discretely for non-Hispanic Black women (0.8 p.p.; 95% CI: -5.4, 7.1) but did for women from other racial/ethnic groups. The decline was larger for women who graduated college (-9.0 p.p.; 95% CI: -12.0, -5.9) than for women without a college degree and for women who were never married (-9.4 p.p., 95% CI: -17.3, -1.5) than for women who were married/partnered or divorced/separated. The USPSTF recommendation to discontinue cervical cancer screening after age 65 leads to a sharp decline in Pap test rates at age 66 but disparately affects women based on race, education and marital status. Further study is needed to assess the consequences of these changes.

HPV vaccination introduction worldwide and WHO and UNICEF estimates of national HPV immunization coverage 2010–2019

WHO/UNICEF estimates for HPV vaccination coverage from 2010 to 2019 are analyzed against the backdrop of the 90% coverage target for HPV vaccination by 2030 set in the recently approved global strategy for cervical cancer elimination as a public health problem. As of June 2020, 107 (55%) of the 194 WHO Member States have introduced HPV vaccination. The Americas and Europe are by far the WHO regions with the most introductions, 85% and 77% of their countries having already introduced respectively. A record number of introductions was observed in 2019, most of which in low- and middle- income countries (LMIC) where access has been limited. Programs had an average performance coverage of around 67% for the first dose and 53% for the final dose of HPV. LMICs performed on average better than high- income countries for the first dose, but worse for the last dose due to higher dropout. Only 5 (6%) countries achieved coverages with the final dose of more than 90%, 22 countries (21%) achieved coverages of 75% or higher while 35 (40%) had a final dose coverage of 50% or less. When expressed as world population coverage (i.e., weighted by population size), global coverage of the final HPV dose for 2019 is estimated at 15%. There is a long way to go to meet the 2030 elimination target of 90%. In the post-COVID era attention should be paid to maintain the pace of introductions, specially ensuring the most populous countries introduce, and further improving program performance globally.

From cervical cancer elimination to eradication of vaccine-type human papillomavirus: Feasibility, public health strategies and cost-effectiveness

The Director-General of the World Health Organization has called for global action towards elimination of cervical cancer as a public health problem. Cervical cancer is caused by human papillomavirus (HPV), an infectious agent with no non-human reservoir. One way to achieve this is through very high levels of vaccine coverage that could enable global eradication of vaccine-type HPV. Using the case study of India, we show that HPV eradication can meet all the Dahlem and Strüngmann criteria for feasibility of eradication. It can be achieved with 90% gender-neutral HPV vaccine coverage together with 95% coverage in high-risk groups such as female sex workers. Such a strategy would likely be cost-effective compared to no vaccination. Although it would be more costly in the short-term than achieving cervical cancer elimination alone, it would save costs in the long-term by removing or at least sharply reducing the need for preventive measures.

Prospects for accelerated elimination of cervical cancer

Human Papillomavirus (HPV) infection is a necessary risk factor for cervical cancer. If HPV is no longer spread, no new cervical cancer precursors will occur. The timepoint for control of the HPV infection will therefore be a rate-limiting step for cervical cancer elimination. We used a validated dynamic HPV transmission model to estimate the age-specific HPV16 incidences and basic reproductive numbers (R0) with input data from Sweden. If R0 is below 1, a fade-out resulting in extinction is expected. Above age 35, we found an R0 of 0.4. Thus, when younger birth cohorts no longer transmit HPV to women >35 years of age, we predict that the HPV infection will no longer be sustained among the older women. Given adequate resources, campaigns to eliminate HPV that are designed based on the R0 measurements followed by screening to detect and treat pre-existing cervical cancer precursors could achieve accelerated cervical cancer elimination.

STRIDES - STudying Risk to Improve DisparitiES in Cervical Cancer in Mississippi – Design and baseline results of a Statewide Cohort Study

Cervical cancer rates in Mississippi are disproportionately high, particularly among Black individuals; yet, research in this population is lacking. We designed a statewide, racially diverse cohort of individuals undergoing cervical screening in Mississippi. Here, we report the baseline findings from this study. We included individuals aged 21 years and older undergoing cervical screening with cytology or cytology-human papillomavirus (HPV) co-testing at the Mississippi State Health Department (MSDH) and the University of Mississippi Medical Center (UMMC) (December 2017-May 2020). We collected discarded cytology specimens for future biomarker testing. Demographics and clinical results were abstracted from electronic medical records and evaluated using descriptive statistics and chi-square tests. A total of 24,796 individuals were included, with a median age of 34.8 years. The distribution of race in our cohort was 60.2% Black, 26.4% White, 7.5% other, and 5.9% missing. Approximately 15% had abnormal cytology and, among those who underwent co-testing at MSDH (n = 6,377), HPV positivity was 17.4% and did not vary significantly by race. Among HPV positives, Black individuals were significantly less likely to be HPV16/18 positive and more likely to be positive for other high-risk 12 HPV types compared to White individuals (20.5% vs. 27.9%, and 79.5% and 72.1%, respectively, p = 0.011). Our statewide cohort represents one of the largest racially diverse studies of cervical screening in the U.S. We show a high burden of abnormal cytology and HPV positivity, with significant racial differences in HPV genotype prevalence. Future studies will evaluate cervical precancer risk, HPV genotyping, and novel biomarkers in this population.

National implementation of HPV vaccination programs in low-resource countries: Lessons, challenges, and future prospects

More than 90% of cervical cancer deaths occur in low- and middle-income countries (LMICs), which have limited capacity to mount the comprehensive national screening and precancer treatment programs that could prevent most of these deaths. The development of vaccines against the human papillomavirus (HPV) has dramatically altered the landscape of cervical cancer prevention. As of mid-2020, 56 LMICs (41% of all LMICs) have initiated national HPV vaccination programs. This paper reviews the experience of LMICs that have introduced HPV vaccine into their national programs, key lessons learned, HPV vaccination sustainability and scale-up challenges, and future mitigation measures. As international guidance evolved and countries accumulated experience, strategies for national introduction shifted with regard to target groups, delivery site and timing, preparation and planning, communications and social mobilization, and ultimately monitoring, supervision and evaluation. Despite the successes that LMICs have been able to achieve in reaching large proportions of eligible girls, there are still considerable challenges countries encounter in overcoming rumors, reaching out-of-school girls, completing the vaccine series, estimating target populations, monitoring program performance, and assuring vaccination sustainability. New opportunities, such as the entry of additional vaccine manufacturers and ongoing studies to evaluate one-dose delivery, could help overcome the outstanding barriers to higher coverage and financial sustainability. Effective use of the experience to date and advances on the horizon could enable all LMICs to move towards the coverage levels that are needed to achieve eventual elimination.

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.

A proposed new generation of evidence-based microsimulation models to inform global control of cervical cancer

Health decision models are the only available tools designed to consider the lifetime natural history of human papillomavirus (HPV) infection and pathogenesis of cervical cancer, and the estimated long-term impact of preventive interventions. Yet health decision modeling results are often considered a lesser form of scientific evidence due to the inherent needs to rely on imperfect data and make numerous assumptions and extrapolations regarding complex processes. We propose a new health decision modeling framework that de-emphasizes cytologic-colposcopic-histologic diagnoses due to their subjectivity and lack of reproducibility, relying instead on HPV type and duration of infection as the major determinants of subsequent transition probabilities. We posit that the new model health states (normal, carcinogenic HPV infection, precancer, cancer) and corollary transitions are universal, but that the probabilities of transitioning between states may vary by population. Evidence for this variability in host response to HPV infections can be inferred from HPV prevalence patterns in different regions across the lifespan, and might be linked to different average population levels of immunologic control of HPV infections. By prioritizing direct estimation of model transition probabilities from longitudinal data (and limiting reliance on model-fitting techniques that may propagate error when applied to multiple transitions), we aim to reduce the number of assumptions for greater transparency and reliability. We propose this new microsimulation model for critique and discussion, hoping to contribute to models that maximally inform efficient strategies towards global cervical cancer elimination.

The role and utility of population-based cancer registries in cervical cancer surveillance and control

Population-based cancer registries (PBCR) are vital to the assessment of the cancer burden and in monitoring and evaluating national progress in cervical cancer surveillance and control. Yet the level of their development in countries exhibiting the highest cervical cancer incidence rates is suboptimal, and requires considerable investment if they are to document the impact of WHO global initiative to eliminate cervical cancer as a public health problem. As a starting point we propose a comprehensive cancer surveillance framework, positioning PBCR in relation to other health information systems that are required across the cancer control continuum. The key concepts of PBCR are revisited and their role in providing a situation analysis of the scale and profile of the cancer-specific incidence and survival, and their evolution over time is illustrated with specific examples. Linking cervical cancer data to screening and immunization information systems enables the development of a comprehensive set of measures capable of assessing the short- and long-term achievements and impact of the initiative. Such data form the basis of national and global estimates of the cancer burden and permit comparisons across countries, facilitating decision-making or triggering cancer control action. The initiation and sustainable development of PBCR must be an early step in the scale-up of cervical cancer control activities as a means to ensure progress is successfully monitored and appraised.

Impact and cost-effectiveness of strategies to accelerate cervical cancer elimination: A model-based analysis

Following the global call for action by the World Health Organization to eliminate cervical cancer (CC), we evaluated how each CC policy decision in Norway influenced the timing of CC elimination, and whether introducing nonavalent human papillomavirus (HPV) vaccine would accelerate elimination timing and be cost-effective. We used a multi-modeling approach that captured HPV transmission and cervical carcinogenesis to estimate the CC incidence associated with six past and future CC prevention policy decisions compared with a pre-vaccination scenario involving 3-yearly cytology-based screening. Scenarios examined the introduction of routine HPV vaccination of 12-year-old girls with quadrivalent vaccine in 2009, a temporary catch-up program for females aged up to 26 years in 2016-2018 with bivalent vaccine, the universal switch to bivalent vaccine in 2017, expansion to include 12-year-old boys in 2018, the switch from cytology- to HPV-based screening for women aged 34-69 in 2020, and the potential switch to nonavalent vaccine in 2021. Introducing routine female vaccination in 2009 enabled elimination to be achieved by 2056 and prevented 17,300 cases. Cumulatively, subsequent policy decisions accelerated elimination to 2039. According to our modeling assumptions, switching to the nonavalent vaccine would not be considered 'good value for money' at relevant cost-effectiveness thresholds in Norway unless the incremental cost was $19 per dose or less (range: $17-24) compared to the bivalent vaccine. CC control policies implemented over the last decade in Norway may have accelerated the timeframe to elimination by more than 17 years and prevented over 23,800 cases by 2110.

A synthesis of evidence for cancer-specific screening interventions: A Preventive Medicine Golden Jubilee Review

The goal of cancer screening guidelines is to inform health practitioners to practice evidence-based cancer prevention. Cancer screening aims to detect treatable precancerous lesions or early-stage disease to enable actions aimed at decreasing morbidity and mortality. Continuous assessment of the available evidence for or against screening interventions by various organizations often results in conflicting recommendations and create challenges for providers and policymakers. Here we have summarized the current cancer screening recommendations by five leading organizations in North America and Europe: the National Cancer Institute's Physician Data Query (PDQ), the U.S. Preventive Services Task Force (USPSTF), the Canadian Task Force on Preventive Health Care (CTFPHC), the Cochrane Database of Systematic Reviews (CDSR), and the UK National Screening Committee for the National Health Service (UK NSC). All organizations assess evidence based on strength, quality, and quantity, and recommendations are similar although with differences with respect to screening start and stop ages. Recommendations are consistent for colorectal cancer screening with fecal occult blood test or fecal immunochemical test, cervical cancer screening with Pap-test, HPV-test, or co-testing, and breast cancer screening with mammography. However, guidelines vary with respect to age to start and end screening and testing frequency. Tests that have proven to be inefficient or whose use is capable of causing harm are routinely recommended against. Continuous review of screening guidelines is necessary to evaluate the many promising screening tests currently under investigation.

Concurrent participation in breast, cervical, and colorectal cancer screening programmes in Denmark: A nationwide registry-based study

Women in Denmark are invited to breast, cervical, and colorectal cancer screening in their fifties and sixties. We determined the patterns of concurrent participation in the three programmes. Participation in organised cancer screening was determined using the highly complete Danish population and health care registers for all women aged 53-65 years on 31 March 2018 who continuously resided in Denmark since 1 April 2012. Data were linked using unique personal identification numbers. We studied overall and cancer-specific proportions of women undergoing screening for all three, two, one, and none of the cancers. Among all 468,507 women, 406,306 (87%) participated in breast, 345,768 (74%) in cervical, and 316,496 (68%) in colorectal cancer screening. Despite high participation, only 255,698 (55%) women were screened for all three cancers, while 123,469 (26%) were screened for two, 54,538 (12%) for one, and 34,802 (7%) were not screened for any cancer. Cancer-specific patterns were highly heterogeneous across the population but changed little after accounting for women's medical history. A significant proportion of women who are screened for a specific cancer remain unscreened for other cancers. The consistency of these data at the international level requires a reconsideration of invitational practices for organised screening.

Evaluation of co-testing with cytology and human papillomavirus testing in cervical screening

Cervical screening is increasingly switching to human papillomavirus (HPV) testing. In many settings, the switch has involved one or several co-tests (testing using both cytology and HPV) in the screening guidelines, to ensure safety. When Sweden switched to HPV testing in 2015 the guidelines included a co-test at age 41. To evaluate the effect of co-testing, we identified all 208,701 women resident in Sweden who in 2019 were 40-42 years old and thus eligible for co-testing. All cervical samples, the results of the test and of the subsequent biopsies were identified in the Swedish National Cervical Screening Registry. Out of the 10,643 women with co-testing in screening, there were 197 women with a subsequent biopsy with high-grade cervical neoplasia or worse (CIN2+). Among these 197 women, 189 had a screening test positive for both HPV and cytology, 6 women were HPV+/Cyt- and 2 women were HPV-/Cyt+. There were 7115 women with a co-test outside of the screening program. Among these, 325 women had a CIN2+ in histopathology, 290 were double positive, 13 women were cyt+/HPV-, and 11 women each were HPV+/cyt- and HPV-/Cyt-. In summary, the additional yield of CIN2+ with co-testing was 2 cases per 10,643 women as compared with 195/10,643 CIN2+ cases detected with HPV screening alone. However, for cervical samples taken outside the screening program (e.g. taken on a clinical indication) there was an increased yield (314 CIN2+ cases detected with co-testing as compared to 301 cases with HPV screening).

Do age-targeted messages increase cervical screening intentions in women aged 50–64 years with weak positive intentions? A randomised control trial in Great Britain

Over 20% of women aged 50-64 in Britain have not attended cervical screening within the recommended 5-year interval. The aim of the present study was to investigate the impact of five messages, informed using strategies from the Behaviour Change Wheel, on strength of intention to attend cervical screening in women aged 50-64 with weak positive intentions to be screened when next invited. Women were randomised (2:2:1), into one of two intervention groups or a control group. The control group saw basic information about cervical screening. Intervention group 1 saw a social norms message and an outcome expectancy message. Intervention group 2 saw a risk reduction message and a response efficacy message. There was further randomisation within the two intervention groups (1:1) to test the effectiveness of message framing and age-targeted information. Lastly, both intervention groups were randomised (1:1) to see a message acknowledging the possible discomfort associated with screening and offering support, or the support message only. Data were included from 475 women, collected using an online survey in March 2022. Adjusting for baseline intention, social norms (p = .84), outcome expectancy (p = .51), risk reduction (p = .19), response efficacy (p = .23) and discomfort acknowledgement messages (p = .71) had no effect on intention strength. However, there was a significant increase in intention after reading multiple messages. These results suggest that although no single message has a significant impact on intentions, when combined, they may act together to increase intention strength. Further research will understand the impact of these messages when combined in information materials.

Operational experiences from the general implementation of HPV self-sampling to Danish screening non-attenders

The Danish cervical cancer screening program is a cost-free cancer prevention program for all Danish resident women aged 23-64 years. The coverage is 73%, but screening attendance is slowly declining. Notwithstanding, almost half of all newly diagnosed cervical cancers are found amongst screening non-attenders. To increase screening attendance, the Capital Region of Denmark implemented HPV self-sampling as an alternative offer to women not attending the regular screening offer. This was an opt-in offer to 57,717 screening non-attending women in 2017-2018. They received an invitation letter and could opt-in by letter, phone, e-mail, or website. Invitation and return-of-kit reminders were used in the set-up. HPV positive women were recommended to go to their General Practitioner (GP) for a follow-up sample. HPV negative women returned to the ordinary screening program. Of all invited women, 15,501 opted-in (27%). The purpose designed website was the most frequent used method of response, 63% opted in by the HPV-self sampling website. Use of invitation and return-of-kit reminders generated 8.6% and 6.1% additional responses and participation, respectively, underlining the importance of timely communication. Overall, 17% returned the HPV self-sampling kit for analysis. In addition, 14% had a regular clinician collected screening sample after receiving the invitation for self-sampling, leading to a total screening of 31% of the invited women. HPV prevalence was 15% and 92% of the women positive for HPV adhered to the recommended follow-up.

Prevalence of Americans reporting a family history of cancer indicative of increased cancer risk: Estimates from the 2015 National Health Interview Survey

The collection and evaluation of family health history in a clinical setting presents an opportunity to discuss cancer risk, tailor cancer screening recommendations, and identify people with an increased risk of carrying a pathogenic variant who may benefit from referral to genetic counseling and testing. National recommendations for breast and colorectal cancer screening indicate that men and women who have a first-degree relative affected with these types of cancers may benefit from talking to a healthcare provider about starting screening at an earlier age and other options for cancer prevention. The prevalence of reporting a first-degree relative who had cancer was assessed among adult respondents of the 2015 National Health Interview Survey who had never had cancer themselves (n = 27,999). We found 35.6% of adults reported having at least one first-degree relative with cancer at any site. Significant differences in reporting a family history of cancer were observed by sex, age, race/ethnicity, educational attainment, and census region. Nearly 5% of women under age 50 and 2.5% of adults under age 50 had at least one first-degree relative with breast cancer or colorectal cancer, respectively. We estimated that 5.8% of women had a family history of breast or ovarian cancer that may indicate increased genetic risk. A third of U.S. adults who have never had cancer report a family history of cancer in a first-degree relative. This finding underscores the importance of using family history to inform discussions about cancer risk and screening options between healthcare providers and their patients.

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/m

Surveillance systems for monitoring cervical cancer elimination efforts: Focus on HPV infection, cervical dysplasia, cervical screening and treatment

In order to achieve the global elimination of cervical cancer as a public health problem, close surveillance of progress in public health and clinical activities and outcomes across the three pillars of vaccination, screening and treatment will be required. Surveillance should ideally occur within an integrated system that is planned, funded, and regularly evaluated to ensure it is providing timely, accurate and relevant feedback for action. In this paper, we conceptualise the main public health surveillance objectives as process and outcome measures in each of the three pillars. Process measures include coverage/participation measures for vaccination, screening and treatment alongside the ongoing assessment of the quality and reach of these programs and activities. Outcome measures related to the natural history of human papillomavirus (HPV) infection include HPV infection prevalence, precursor cervical lesions and cervical cancers (including stage at diagnosis, cancer incidence and mortality). These outcome measures can be used for monitoring the effectiveness of the three core activities in the short, medium and long term to assess whether these interventions are effectively reducing their occurrence. We discuss possible methods for the surveillance of these measures in the context of country capacity, drawing from examples in Australia, the USA and in low and middle income countries.

Examining aspects of successful community-based programs promoting cancer screening uptake to reduce cancer health disparity: A systematic review

Certain minorities in the US are disproportionately burdened with higher cancer incidence and mortality rates. Programs encouraging timely uptake of cancer screening measures serve to reduce cancer health disparities. A systematic literature review was conducted to assess the effectiveness and the qualities of these programs, and to elucidate characteristics of success programs to aid in designing of future ones. We focused on community-based programs rather than clinic-based programs as the former are more likely to reach disadvantaged populations, and on prevention programs for breast, cervical, and/or colon cancers as longstanding screening recommendations for these cancers exist. PubMed, CINAHL and EBSCO databases were searched for articles that utilized community organizations and community health workers. Fourteen programs described in 34 manuscripts were identified. While 10 of 14 programs reported statistically significant increases in cancer prevention knowledge and/or increase in screening rates, only 7 of them enrolled large numbers of participants (defined as ≥1000). Only 7 programs had control groups, only 4 programs independently verified screening uptake, and 2 programs had long-term follow-up (defined as more than one screening cycle). Only one program demonstrated elimination of cancer health disparity at a population level. While most community-based cancer prevention programs have demonstrated efficacy in terms of increased knowledge and/or screening uptake, scalability and demonstration in reduction at a population level remain a challenge.

Behavioral economics informed message content in text message reminders to improve cervical screening participation: Two pragmatic randomized controlled trials

The objective of the reported research was to assess the impact of text message (SMS) reminders and their content on cervical screening rates. Women invited for cervical screening in Northwest London from February-October 2015 were eligible. 3133 women aged 24-29 (Study 1) were randomized (1, 1) to 'no SMS' (control), or a primary care physician (PCP) endorsed SMS (SMS-PCP). 11,405 women aged 30-64 (Study 2), were randomized (1, 1:1:1:1:1:1) to either: no SMS, an SMS without manipulation (SMS), the SMS-PCP, an SMS with a total or proportionate social norm (SMS-SNT or SMS-SNP), or an SMS with a gain-framed or loss-framed message (SMS-GF and SMS-LF). The primary outcome was participation at 18 weeks. In Study 1 participation was significantly higher in the SMS-PCP arm (31.4%) compared to control (26.4%, aOR, 1.29, 95%CI: 1.09-1·51; p = 0.002). In Study 2 participation was highest in the SMS-PCP (38.4%) and SMS (38.1%) arms compared to control (34.4%), (aOR: 1.19, 95%CI: 1.03-1.38; p = 0.02 and aOR: 1.18, 95%CI: 1.02-1.37; p = 0.03, respectively). The results demonstrate that behavioral SMSs improve cervical screening participation. The message content plays an important role in the impact of SMS. The results from this trial have already been used to designing effective policy for cervical cancer screening. The NHS Cervical Screening Programme started running a London-wide screening SMS campaign which was based on the cervical screening trial described here. According to figures published by Public Health England, after six months attendance increased by 4.8%, which is the equivalent of 13,400 more women being screened at 18 weeks.

Impact of school-based educational interventions in middle adolescent populations (15-17yrs) on human papillomavirus (HPV) vaccination uptake and perceptions/knowledge of HPV and its associated cancers: A systematic review

The American Academy of Paediatrics (AAP) divides adolescence into early (12-14 years), middle (15-17 years), and late (18-21 years) stages. School-based HPV educational interventions are largely directed at parents of early adolescents at the time of vaccination. As the average age of first sexual intercourse in high income countries is 15-17 years old, a second educational intervention for middle adolescents could have a strong impact on HPV prevention, providing an opportunity for self-consenting to HPV vaccination in many countries. This paper appraises literature exploring the impact of school-based educational interventions in 15-17 year olds, on HPV vaccination uptake and/or perceptions/knowledge of HPV and its associated cancers. Randomised controlled trials (RCTs) and quasi-experimental designs (QEDs) (2007-2019) were included if they delivered a school-based educational intervention for 15-17 year olds, and the outcome measures included HPV vaccination uptake, knowledge of HPV and associated cancers or perception/attitude regarding self-protection against HPV. Fifteen studies met the inclusion criteria and were assessed for quality using the Quality Assessment Tool for Quantitative Studies. All studies demonstrated a statistically significant improvement in at least one major outcome measure post-intervention, despite the wide range in design of interventions, though only three studies actually measured changes to HPV vaccination uptake. Stakeholder engagement was absent in most intervention designs and many were not grounded in evidenced theory. Content was largely focused on female cervical cancer, rarely discussing oropharyngeal cancer, the most pre-dominant HPV-associated cancer in men. An optimal mixed gender intervention remains to be established for middle adolescents.

Impact of disruptions and recovery for established cervical screening programs across a range of high-income country program designs, using COVID-19 as an example: A modelled analysis

COVID-19 has disrupted cervical screening in several countries, due to a range of policy-, health-service and participant-related factors. Using three well-established models of cervical cancer natural history adapted to simulate screening across four countries, we compared the impact of a range of standardised screening disruption scenarios in four countries that vary in their cervical cancer prevention programs. All scenarios assumed a 6- or 12-month disruption followed by a rapid catch-up of missed screens. Cervical screening disruptions could increase cervical cancer cases by up to 5-6%. In all settings, more than 60% of the excess cancer burden due to disruptions are likely to have occurred in women aged less than 50 years in 2020, including settings where women in their 30s have previously been offered HPV vaccination. Approximately 15-30% of cancers predicted to result from disruptions could be prevented by maintaining colposcopy and precancer treatment services during any disruption period. Disruptions to primary screening had greater adverse effects in situations where women due to attend for screening in 2020 had cytology (vs. HPV) as their previous primary test. Rapid catch-up would dramatically increase demand for HPV tests in 2021, which it may not be feasible to meet because of competing demands on the testing machines and reagents due to COVID tests. These findings can inform future prioritisation strategies for catch-up that balance potential constraints on resourcing with clinical need.

Cost-effectiveness evidence for HPV self-sampling could be improved by giving greater attention to vulnerable populations

Leveraging vertical COVID-19 investments to improve monitoring of cancer screening programme – A case study from Bangladesh

Cancer screening programs from majority of the low- and middle-income countries (LMICs) report screening coverage as the only performance indicator, and that too measured through population-based sample surveys. Such information is unreliable and has very little value in assessing programmatic quality and impact. Regular monitoring of key process and outcome indicators based on data collected through a robust information system is essential to ensure quality of a screening programme. Fragmented health systems, limited resources and absence of a culture of systematic evaluation are the major hindrances for most of the LMICs to build electronic information systems to manage screening. The COVID-19 pandemic has created an impetus for the countries to customize the freely available District Health Information Software (DHIS2) to collect electronic data to track the outbreaks and manage containment measures. In the present article we present Bangladesh as an exemplar LMIC that has a (DHIS2) based integrated health information system gradually upgraded to collect individual data of the participants to the national cervical cancer screening program. Such efforts paid rich dividends as the screening program was switched from opportunistic to a population-based one. Moreover, the electronic system could report impact of the pandemic on cancer screening on a monthly basis. The aggregate number of women screened in the year 2020 was 14.1% less compared to 2019. The monthly rate of screening during peak of the outbreak was only 5.1% of the previous year. The rate rapidly recovered as the program intensified screening in the hard-to-reach regions less affected by the pandemic and expanded the outreach services. Other LMICs may emulate Bangladesh example. Customizing the information system developed for pandemic surveillance to collect cancer screening data will help them build back the screening programs better.

Is India’s public health care system prepared for cervical cancer screening?: Evaluating facility readiness from the fourth round of the District Level Household and Facility Survey (DLHS-4)

India's cervical cancer screening program was launched in 2016. We evaluated baseline facility readiness using nationally representative data from the 2012-13 District Level Household and Facility Survey on 4 tiers of the public health care system - 18,367 sub-health centres (SHCs), 8540 primary health centres (PHCs), 4810 community health centres and 1540 district/sub-divisional hospitals. To evaluate facility readiness we used the Improving Data for Decision Making in Global Cervical Cancer Programmes toolkit on six domains - potential staffing, infrastructure, equipment and supplies, infection prevention, medicines and laboratory testing, and data management. Composite scores were created by summing responses within domains, standardizing scores across domains at each facility level, and averaging across districts/states. Overall, readiness scores were low for cervical cancer screening. At SHCs, the lowest scores were observed in 'infrastructure' (0.55) and 'infection prevention' (0.44), while PHCs had low 'potential staffing' scores (0.50) due to limited manpower to diagnose and treat (cryotherapy) potential cases. Scores were higher for tiers conducting diagnostic work-up and treatment/referral. The highest scores were in 'potential staffing' except for PHCs, while the lowest scores were in 'infection & prevention' and 'medicines and laboratory'. Goa and Maharashtra were consistently among the top 5 ranking states for readiness. Substantial heterogeneity in facility readiness for cervical cancer screening spans states and tiers of India's public healthcare system. Infrastructure and staffing are large barriers to screening at PHCs, which are crucial for referral of high-risk patients. Our results suggest focus areas in cervical cancer screening at the district level for policy makers.

Combined patterns of participation in cervical, breast, and colorectal cancer screenings and factors for non-participation in each screening among women in Japan

Finding effective strategies to increase participation in cervical cancer screening (CCS), breast cancer screening (BCS) and colorectal cancer screening (CRCS) for women is an important public health issue. Our objective was to examine combined patterns of participation in these three screenings and investigate the factors associated with non-participation in each. We analyzed 115,254 women aged 40-69 who were age-eligible for all three screenings from a 2016 nationally representative cross-sectional survey in Japan. Eight screening patterns were defined as full-participation (CCS + BCS + CRCS), partial-participation (CCS + BCS, CCS + CRCS, BCS + CRCS, CCS, BCS, CRCS), and non-participation (none). Multinomial logistic regression analysis adjusted for age, marital status, educational attainment, employment status, self-rated health, current hospital visits, and smoking status was performed to evaluate the factors associated with each screening pattern, using full-participation as the reference category. Screening rates for cervical, breast, and colorectal cancer were 45.0%, 46.2%, and 40.4%, respectively. Although only 26.9% of women participated in all three screenings, more than 60% participated in at least one screening. Unstable employment, low educational attainment, low self-rated health, and current smoker were associated with both non-participation and partial-participation, especially single-participation in cervical and breast cancer screening. For example, self-employed women were more likely to be non-participants [aOR 2.80 95%CI: 2.65-2.96], single-participants for CCS [aOR 2.87 95%CI: 2.57-3.20], and BCS [aOR 2.07 95%CI: 1.85-2.33] than permanent workers. It may be useful to consider related factors for non-participation patterns to encourage partial-participants to have other cancer screenings by utilizing one cancer screening as an opportunity to provide information about other screenings.

Non-participation in cervical cancer screening according to health, lifestyle and sexual behavior: A population-based study of nearly 15,000 Danish women aged 23–45 years

High participation in cervical cancer screening is essential for an effective screening program. In this population-based study, we investigated associations between general health, lifestyle and sexual behavior, and non-participation in cervical cancer screening in Denmark. During 2011-2012, a random sample of women aged 18-45 years from the general female population were invited to participate in a survey regarding health, lifestyle and sexual habits. Altogether 18,631 women responded (response rate: 75.1%), of whom 14,271 women aged 23-45 years were included in this analysis. Information on screening participation within four years after response, and data on sociodemographic characteristics, was obtained from nationwide registers. Logistic regression was used to calculate odds ratios (ORs) for non-participation, crude and adjusted for sociodemographic characteristics. Overall, 13.9% of the women were not screened during follow-up. The odds of non-participation was increased in women who were overweight (OR

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

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. 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. 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. 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.

Authors' response: Cost-effectiveness evidence for HPV self-sampling could be improved by giving greater attention to vulnerable populations

Are uninsured women in a national screening program having longer intervals between cervical cancer screening tests?

With increased understanding of the natural history of cervical cancer, cervical cancer screening recommendations have evolved (Schiffman & Wentzensen, 2013). As research better quantified the balance of benefits and harms of screening, new recommendations called for longer intervals between screening tests. Adherence to longer screening intervals detects similar numbers of abnormalities and decreases harms associated with overscreening/overtreatment. In this descriptive study, we examined the cervical cancer screening intervals from 2010 to 2018 in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). There were 1,397,899 women aged 21-64 who were screened for cervical cancer from 2010 to 2018 and 556,743 rescreenings of average risk women were performed. The median cervical screening interval increased from 2.02 years in 2010 to 3.88 years in 2018. Providers serving uninsured women in a national screening program are following the recommendations of longer intervals between cervical cancer screenings.

Barriers and facilitators to cervical cancer screening among transgender men and non-binary people with a cervix: A systematic narrative review.

Cervical cancer mortality in the United Kingdom (UK) has decreased over the last decade, largely due to uptake of cervical cancer screening. However, only those with a female gender marker on their health records are invited, creating a significant barrier to gender minorities accessing screening. We undertook a systematic review to synthesise published literature on cervical cancer screening among eligible gender minorities, aiming to identify barriers and facilitators that might inform changes in UK policy and clinical practice. We conducted a broad search across Medline, Embase, PsycInfo and Global Health databases to 3rd January 2020 and included any original, peer-reviewed research, published in the English language that reported on cervical cancer screening among gender minorities assigned female at birth (AFAB). Twenty-seven studies were critically appraised and included in the final synthesis, which identified significant disparities in cervical cancer screening uptake between gender minorities AFAB and cis women. It revealed a lack of knowledge surrounding the relationship between gender minority status and cervical cancer risk among both service users and providers and highlighted significant barriers to access for gender minorities AFAB. Cervical cancer screening was not universally associated with dysphoria among gender minorities AFAB and we recommend that providers explore patients' preferences around screening, while avoiding assumptions. Providers should be proficient in examination techniques that maximise patient autonomy and minimise gender dysphoria or pain. Self-swabs for high-risk HPV may provide a more acceptable, evidence-based, alternative to Pap smears but there remains a need for further UK-specific research, to inform changes in policy.

The cost-effectiveness of human papillomavirus self-collection among cervical cancer screening non-attenders in El Salvador

Cervical cancer screening with human papillomavirus (HPV) DNA testing has been incorporated into El Salvador's national guidelines. The feasibility of home-based HPV self-collection among women who do not attend screening at the clinic (i.e., non-attenders) has been demonstrated, but cost-effectiveness has not been evaluated. Using cost and compliance data from El Salvador, we informed a mathematical microsimulation model of HPV infection and cervical carcinogenesis to conduct a cost-effectiveness analysis from the societal perspective. We estimated the reduction in cervical cancer risk, lifetime cost per woman (2017 US$), life expectancy, and incremental cost-effectiveness ratio (ICER, 2017 US$ per year of life saved [YLS]) of a program with home-based self-collection of HPV (facilitated by health promoters) for the 18% of women reluctant to screen at the clinic. The model was calibrated to epidemiologic data from El Salvador. We evaluated health and economic outcomes of the self-collection intervention for women aged 30 to 59 years, alone and in concert with clinic-based HPV provider-collection. Home-based self-collection of HPV was projected to reduce population cervical cancer risk by 14% and cost $1210 per YLS compared to no screening. An integrated program reaching 99% coverage with both provider- and home-based self-collection of HPV reduced cancer risk by 74% (compared to no screening), and cost $1210 per YLS compared to provider-collection alone. Self-collection facilitated by health promoters is a cost-effective strategy for increasing screening uptake in El Salvador.

Risk prediction of cervical abnormalities: The value of sociodemographic and lifestyle factors in addition to HPV status

High-risk human papillomavirus (hrHPV) assessment as a primary screening test improves sensitivity but decreases specificity. Determining risk for cervical abnormalities and adapting policy accordingly may improve the balance between screening benefits and harms. Our aim is to assess the value of factors other than HPV in prediction of cervical abnormalities. Data from a Dutch prospective cohort were used. Women aged 18-29 years, not yet eligible for screening, were included in 2007. Data collection consisted of a questionnaire and a cervicovaginal self-sample. Linkage with PALGA (pathology database) was performed in 2017. The analyses included 1483 women. The full model, including sociodemographic and lifestyle factors, was compared to the null model, including baseline HPV only. The outcome of interest was cervical intraepithelial neoplasia 2 or worse (CIN2+). There were 86 women with CIN2+. Baseline hrHPV status was an important predictor (OR = 5.20, 95%CI = 3.27-8.27). The area under the ROC curve (AUC) of the null model was 0.67 (95%CI = 0.61-0.72). The full model had a slightly higher AUC of 0.73 (95%CI = 0.67-0.79). Bootstrap validation indicated that overfitting was present. This exploratory study has confirmed that a single hrHPV measurement is a strong predictor of cervical abnormalities, and additional risk factors in young women appeared to have limited added value. However, prediction based on hrHPV only does leave room for improvement. Future studies should therefore focus on women in the screening age range and search for other predictors to further enhance risk prediction. Adapting policy based on risk may eventually help optimise screening performance.

Exacerbating disparities?: Cervical cancer screening and HPV vaccination

The human papillomavirus (HPV) vaccine is a powerful tool in cancer prevention. In combination with cervical cancer screening programs, this vaccine has the potential to nearly eliminate death from cervical cancer. However, this remarkable public health success can only be realized if vaccines reach those most at risk-unscreened women. Vaccinating only those already well-screened would have little impact on cervical cancer mortality, exacerbate disparities, and be a striking public health failure. We use data from the Behavioral Risk Factor Surveillance System optional Adult HPV Vaccination module between 2013 and 2016 to assess the association between HPV vaccine status and cervical cancer screening behavior. Only 27% of eligible women had received any HPV vaccination. Uninsured women were less likely to be vaccinated (aOR: 0.48, 95% CI:0.30-0.76) and less likely to be screened (aOR: 0.41, 95% CI:0.28-0.60) than insured women. Vaccinated women were more than twice as likely to be up to date on screening than unvaccinated women (aOR: 2.14, 95% CI:1.46-3.12). Younger women were 49% less likely to be up to date on screening (aOR: 0.51, 95% CI:0.37-0.71), but over 4 times more likely to be vaccinated (aOR: 4.44, 95% CI:3.20-6.17) than older women. Unvaccinated, unscreened women are at continued risk for cervical cancer. Uninsured women were most likely to be in this group. Concerted efforts should be focused on increasing vaccination and screening in this population. Cancer prevention innovations, like the HPV vaccine, must reach at-risk populations to avoid further protecting the protected and failing to reduce existing health disparities.

Trends in HPV- and non-HPV-associated vulvar cancer incidence, United States, 2001–2017

Vulvar cancer incidence has been rising in recent years, possibly due to increasing exposure to human papillomavirus (HPV). We assessed incidence rates of HPV-associated and non-HPV-associated vulvar cancers diagnosed from 2001 to 2017 in the United States (US). Using population-based cancer registry data covering 99% of the US population, incidence rates were calculated and stratified by age, race/ethnicity, stage, geographic region, and histology. The average annual percent change in incidence per year were calculated using joinpoint regression. From 2001 to 2017, the incidence of HPV-associated vulvar cancers increased by 1.2% per year, most notably among women who were aged 50-59 years (2.6%), 60-69 years (2.4%), and ≥ 70 years (0.9%); of White (1.5%) and Black (1.1%) race; diagnosed at an early (1.3%) and late (1.8%) stage; and living in the Midwest (1.9%), Northeast (1.4%), and South (1.2%). Incidence increased each year for HPV-associated histologic subtypes including keratinizing (4.7%), non-keratinizing (6.0%), and basaloid (3.1%) squamous cell carcinomas (SCCs), while decreases were found in warty (2.7%) and microinvasive (5.5%) SCCs. HPV-associated vulvar cancer incidence increased overall and among women aged over 50 years while remaining stable among women younger than 50 years. The overall incidence for non-HPV-associated cancers was stable. Continued surveillance of HPV-associated cancers will allow us to monitor future trends as HPV vaccination coverage increases in the US.

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.

Comparative assessment of test characteristics of cervical cancer screening methods for implementation in low-resource settings

Cervical cancer disproportionately affects low-resource settings. Papanicolaou, human papillomavirus (HPV), and visual inspection of cervix with acetic acid (VIA) testing, each with different characteristics, will reduce cervical cancer burden. We conducted a critical literature review using PubMed, Cochrane, WHO, and grey literature from 1994 to 2020. We examined efficacy, harms, and comparative effectiveness of screening methods by age, human immunodeficiency virus, provider characteristics, and assessed implementation challenges in low-resource settings. Comprehensive data on utility and efficacy of screening tests indicates that each screening has strengths and shortcomings but all confer acceptable performance. HPV and VIA appear more promising. Primary HPV test-and-treat, self-testing, and co-testing have been studied but data on triage plans, cost, support system, implementation and sustainability is unclear in low-resource settings. HPV testing could help target subgroups of older or higher risk women. VIA offers local capacity-building and scalability. Quality VIA technique after HPV testing is still required to guide post-screening treatments. VIA competencies decline gradually with current standard trainings. Stationary cervicography improves VIA quality but isn't scalable. Affordable smartphones eliminate this barrier, enhance training through mentorship, and advance continuing education and peer-to-peer training. Smartphone-based VIA facilitates cervical image storage for patient education, health promotion, record-keeping, follow-up care, remote expert support, and quality control to improve VIA reliability and reproducibility and reduce mis-diagnoses and burden to health systems. Rather than ranking screening methods using test characteristics alone in study or higher-resource settings, we advocate for scalable strategies that maximize reliability and access and reduce cost and human resources.

Intentions to participate in cervical and colorectal cancer screening during the COVID-19 pandemic: A mixed-methods study

Worldwide, cancer screening faced significant disruption in 2020 due to the COVID-19 pandemic. If this has led to changes in public attitudes towards screening and reduced intention to participate, there is a risk of long-term adverse impact on cancer outcomes. In this study, we examined previous participation and future intentions to take part in cervical and colorectal cancer (CRC) screening following the first national lockdown in the UK. Overall, 7543 adults were recruited to a cross-sectional online survey in August-September 2020. Logistic regression analyses were used to identify correlates of strong screening intentions among 2319 participants eligible for cervical screening and 2502 eligible for home-based CRC screening. Qualitative interviews were conducted with a sub-sample of 30 participants. Verbatim transcripts were analysed thematically. Of those eligible, 74% of survey participants intended to attend cervical screening and 84% intended to complete home-based CRC screening when next invited. Thirty percent and 19% of the cervical and CRC samples respectively said they were less likely to attend a cancer screening appointment now than before the pandemic. Previous non-participation was the strongest predictor of low intentions for cervical (aOR 26.31, 95% CI: 17.61-39.30) and CRC (aOR 67.68, 95% CI: 33.91-135.06) screening. Interview participants expressed concerns about visiting healthcare settings but were keen to participate when screening programmes resumed. Intentions to participate in future screening were high and strongly associated with previous engagement in both programmes. As screening services recover, it will be important to monitor participation and to ensure people feel safe to attend.

Associations of steps per day and step intensity with the risk of cancer: Findings from the Women's Health Accelerometry Collaboration cohort

Clinical follow-up practices after cervical cancer screening by co-testing: A population-based study of adherence to U.S. guideline recommendations

Failure to follow-up women after abnormal cervical screening could lead to cervical cancers, yet little is known about adherence to recommended follow-up after abnormal co-testing [cytology and high-risk human papillomavirus (hrHPV) testing]. We documented clinical management following cervical screening by co-testing in a diverse population-based setting. A statewide surveillance program for cervical screening, diagnosis, and treatment was used to investigate all cytology, hrHPV and biopsy reports in the state of New Mexico from January 2015 through August 2019. Guideline-adherent follow-up after co-testing required 1) biopsy within 6 months for low-grade cytology if positive for hrHPV, for high-grade cytology irrespective of hrHPV, and for HPV 16/18 positive results irrespective of cytology and; 2) repeat co-testing within 18 months if cytology was negative and hrHPV test was positive (excluding types 16/18). Screening co-tests (2015-2017) for 164,522 women were analyzed using descriptive statistics, Kaplan Meier curves, and pairwise comparisons between groups. Guideline adherence was highest when both cytology and hrHPV tests were abnormal, ranging from 61.7% to 80.3%. Guideline-adherent follow-up was lower for discordant results. Women with high-grade cytology were less likely to receive a timely biopsy when hrHPV-testing was negative (48.1%) versus positive (83.3%) (p < 0.001). Only 47.9% of women received biopsies following detection of HPV16/18 with normal cytology, and 30.8% received no follow-up within 18-months. Among women with hrHPV-positive normal cytology without evidence of HPV 16/18 infection, 51% received no follow-up within 18 months. Provider education and creation of robust recall systems may help ensure appropriate follow-up of abnormal screening results.

Mortality trends and disease burdens of cervical, endometrial and ovarian cancers from 1981 to 2020 in Taiwan

Cervical, endometrial, and ovarian cancers are major gynecologic cancers in Taiwan. Although cervical cancer has received attention through nationwide screening program and the rollout of the human papillomavirus vaccine, endometrial and ovarian cancers have attracted less attention. The age-period-cohort analysis of constant-relative-variation method was used to estimate the mortality trends of cervical, endometrial, and ovarian cancers for population aged 30-84 years during 1981-2020 in Taiwan. The years of life lost was used to estimate the disease burden due to premature death from gynecological cancers. The age effect of endometrial cancer mortality was greater than those of cervical and ovarian cancers. The period effects decreased during 1996-2000 for cervical cancer and plateaued for endometrial and ovarian cancers during 2006-2020. The cohort effect decreased after the birth year 1911 for cervical cancer, increased after 1931 for endometrial cancer, and increased in all birth years for ovarian cancer. For both endometrial and ovarian cancers, the Spearman's correlation coefficients revealed the strong negative correlations between the fertility and the cohort effects, and the strong positive correlations between the average age at first childbirth and the cohort effects. The burden of premature death from ovarian cancer was higher than those of cervical and endometrial cancers during 2016-2020. Due to increasing cohort effect and burden of premature death, endometrial and ovarian cancers will become the largest threat to women's reproductive health in Taiwan.