JNCI Cancer Spectrum

Political determinants of US states’ screening-amenable cancer stage at diagnosis and premature cancer mortality

Abstract Background Political determinants of cancer risk are largely unexplored, conceptually and empirically. Methods Observational analysis of associations present in 2017-2021 between 5 state-level political metrics and 4 age-standardized cancer outcomes (regional and distant stage at diagnosis for breast, cervical, and colorectal cancer among screening-age adults and premature cancer mortality), overall and in standardized linear regression models adjusting for state-level poverty and medical uninsurance. Results In fully adjusted models (adjusted for state-level poverty and state-level medical uninsurance variables: % working age adults [age 35-64] without medical insurance; number of years of state Medicaid expansion), each 1 SD shift toward a more liberal political ideology (measured by voting record) among elected officials in the US House of Representatives was associated with decreased risk of diagnosis with regional and distant breast and colorectal cancer (respectively: −0.76, 95% confidence interval [CI] = −1.26 to −0.25; −0.75; 95% CI = −1.5 to 0). Risk of premature cancer mortality likewise was lower, in the fully adjusted models, with each 1 SD shift toward more liberal scores for the state electoral college vote (−2.01, 95% CI = −3.68 to −0.33), the state liberalism policy index (−2.51, 95% CI = −4.48 to −0.54), and political ideology of elected officials in the US Senate (−1.93, 95% CI = −3.71 to −0.14). Conclusion Our state-level analyses suggest that political metrics are associated with preventable cancer outcomes. Efforts to reduce population burdens of cancer and inequities in these burdens could benefit from analyses of sociopolitical drivers of cancer risk across the cancer continuum.

Increased colorectal and endometrial cancer rates in a genomically ascertained Lynch syndrome cohort

Abstract Background Lynch syndrome (LS) is a hereditary cancer predisposition that increases risk for colorectal, endometrial, and other cancers. Although population-based genomic screening programs identify individuals with LS, clinical presentation in such genomically ascertained populations is unknown. Methods MyCode is a healthcare system-based biobank that returns clinically actionable genomic screening results to participants, including pathogenic/likely pathogenic (P/LP) variants in LS genes (MLH1, MSH2, MSH6, PMS2). Adult cases (participants with an LS result) and controls (participants without a cancer predisposition variant matched to cases) reported their personal and family cancer histories. Rates of meeting National Comprehensive Cancer Network (NCCN) genetic testing guidelines and rates of colorectal and endometrial cancers in cases, controls, and their family members were calculated and compared. Results A total of 175 cases (10 MLH1, 7 MSH2, 83 MSH6, and 75 PMS2) and 169 controls were included. Of case pedigrees, 62/175 (35.4%) met NCCN criteria for LS evaluation. Case pedigrees were more likely (P < .001) to meet criteria than control pedigrees (4/169, 8.35%). Case probands had significantly higher rates of colorectal and endometrial cancer than controls (7.7% vs 2.4%, P = .03 colorectal; 11.5% vs 0%, P < .001 endometrial), as did their relatives (3.1% vs 0.9%, P < .001 colorectal; 2.2% vs 0.5%, P < .001 endometrial). Conclusions NCCN guidelines missed 65% of cases with P/LP LS variants despite families having higher colorectal and endometrial cancer rates compared with controls. Genomic screening can assist in identifying individuals at risk for LS-related cancers, providing an opportunity to tailor risk management for cancer prevention and early detection.

Lifestyle and environmental factors in women carrying BRCA pathogenic variants with and without cancer

Abstract Background In the development of breast cancer and ovarian cancer there may be an influence of lifestyle and environmental factors. This influence could be relevant also in patients with genetic predisposition such as in carriers of germline pathogenic variants in the BRCA genes. However, this issue has been addressed in only a few studies so far. Methods In this retrospective, multicenter case-control study, we enrolled participants with a pathogenic variant BRCA gene and divided into 2 groups: group 1, patients with breast cancer and/or ovarian cancer, and group 2, subjects without cancer. We compared these groups regarding demographic data as age, body mass index, smoking habits, estroprogestinic use, Mediterranean diet, and physical activity. Multivariable analyses were used to identify predisposing factors. All evaluations were 2-tailed and considered statistically significant if the P value was less than .05. Results We enrolled 281 participants, 135 (79.4%) with breast cancer, 32 (18.8%) with ovarian cancer, 3 (1.8%) with both, and 111 unaffected (39.5%) women. Independent risk factors associated with cancer were age (P < .0001); body mass index (P = .007); family history (P = .002); occupation (P = .003); smoking habits (P = .012), number of cigarettes smoked (P = .016), and pack-year index (P = .022); and estroprogestinic use (P = .032) and years of estroprogestinic use (P = .029). At multivariate analysis, age (odds ratio [OR] = 1.062; P < .0001), family history (OR = 0.129; P = .001), number of cigarettes smoked (P = .014), and estroprogestinic use (OR = 2.009; P = .025) were statistically significant risk factors associated with cancer development. Conclusions In the development of breast cancer and ovarian cancer, lifestyle and environmental factors seem to play a statistically significant role in the presence of genetic predisposition associated with BRCA1 and BRCA2 gene mutations.

Easy ensemble classifier-group and intersectional fairness and threshold (EEC-GIFT): a fairness-aware machine learning framework for lung cancer screening eligibility using real-world data

Abstract Background We use real-world data to develop a lung cancer screening (LCS) eligibility mechanism that is both accurate and free from racial bias. Methods Our data came from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. We built a systematic fairness-aware machine learning framework by integrating a Group and Intersectional Fairness and Threshold (GIFT) strategy with an easy ensemble classifier—(EEC-) or logistic regression—(LR-) based model. The best LCS eligibility mechanism EEC-GIFT* and LR-GIFT* were applied to the testing dataset and their performances were compared to the 2021 US Preventive Services Task Force (USPSTF) criteria and PLCOM2012 model. The equal opportunity difference (EOD) of developing lung cancer between Black and White smokers was used to evaluate mechanism fairness. Results The fairness of LR-GIFT* or EEC-GIFT* during training was notably greater than that of the LR or EEC models without greatly reducing their accuracy. During testing, the EEC-GIFT* (85.16% vs 78.08%, P < .001) and LR-GIFT* (85.98% vs 78.08%, P < .001) models significantly improved sensitivity without sacrificing specificity compared to the 2021 USPSTF criteria. The EEC-GIFT* (0.785 vs 0.788, P = .28) and LR-GIFT* (0.785 vs 0.788, P = .30) showed similar area under receiver operating characteristic curve values compared to the PLCOM2012 model. While the average EODs between Blacks and Whites were significant for the 2021 USPSTF criteria (0.0673, P < .001), PLCOM2012 (0.0566, P < .001), and LR-GIFT* (0.0081, P < .001), the EEC-GIFT* model was unbiased (0.0034, P = .07). Conclusion Our EEC-GIFT* LCS eligibility mechanism can significantly mitigate racial biases in eligibility determination without compromising its predictive performance.

Fertility preservation and in vitro fertilization (IVF) success rates after cancer

Abstract Background Evidence of the success of in vitro fertilization (IVF) procedures is critical for informed decision making before and after cancer treatment. We compared IVF outcomes between women with and without cancer. Methods Using data from a national IVF database—the Society for Assisted Reproductive Clinic Outcomes Reporting System, linked to statewide cancer registries and birth certificates in 9 states—we identified women who initiated IVF after a cancer diagnosis. Fertility preservation was defined as oocyte retrieval ≤90 days after cancer diagnosis, and IVF after cancer treatment as retrieval >90 days postdiagnosis. Number of oocytes retrieved and conception and livebirth rates were compared between these groups and a comparison group of women without cancer in couples with male factor infertility only. Results Compared with retrievals for male factor infertility only (n = 81 370), the number of oocytes retrieved was not significantly different for women who underwent retrieval for fertility preservation (n = 2941) but was significantly lower for women who underwent retrievals after cancer treatment (n = 2479) (mean difference = −2.99, 95% confidence interval [CI] = −3.40 to 2.59). Rate of conception as a function of transfer attempts and likelihood of livebirth after conception also did not significantly differ for fertility preservation (n = 291) compared with male factor infertility only (n = 34 410). Women with IVF after cancer treatment (n = 672) had a lower rate of conception (hazard ratio = 0.70, 95% CI = 0.61 to 0.79) but a similar overall likelihood of a livebirth after conception, relative to the group with male factor infertility only. Conclusion IVF outcomes may be maximized when ovarian retrieval is initiated before cancer treatment.

The genomic landscape of breast and non-breast cancers from individuals with germline CHEK2 deficiency

Abstract CHEK2 is considered to be involved in homologous recombination repair (HRR). Individuals who have germline pathogenic variants (gPVs) in CHEK2 are at increased risk to develop breast cancer and likely other primary cancers. PARP inhibitors (PARPi) have been shown to be effective in the treatment of cancers that present with HRR deficiency—for example, caused by inactivation of BRCA1/2. However, clinical trials have shown little to no efficacy of PARPi in patients with CHEK2 gPVs. Here, we show that both breast and non-breast cancers from individuals who have biallelic gPVs in CHEK2 (germline CHEK2 deficiency) do not present with molecular profiles that fit with HRR deficiency. This finding provides a likely explanation why PARPi therapy is not successful in the treatment of CHEK2-deficient cancers.

The survival benefit associated with complete macroscopic resection in epithelial ovarian cancer is histotype specific

Abstract Background Complete macroscopic resection is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high-grade serous ovarian carcinoma, and the benefit of complete macroscopic resection in other histotypes is poorly characterized. We sought to determine which histotypes derive the greatest benefit from complete macroscopic resection to better inform future decisions on radical cytoreductive efforts. Methods We performed multivariable analysis of disease-specific survival across 2 independent patient cohorts to determine the magnitude of benefit associated with complete macroscopic resection within each histotype. Results Across both cohorts (Scottish: n = 1622; Surveillance, Epidemiology, and End Results [SEER]: n = 18 947), complete macroscopic resection was associated with prolonged disease-specific survival; this was more marked in the Scottish cohort (multivariable hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.37 to 0.52 vs HR = 0.59, 95% CI = 0.57 to 0.62 in SEER). In both cohorts, clear cell ovarian carcinoma was among the histotypes to benefit most from complete macroscopic resection (multivariable HR = 0.23 and HR = 0.50 in Scottish and SEER cohorts, respectively); high-grade serous ovarian carcinoma patients demonstrated highly statistically significant and clinically meaningful survival benefit, but this was of lower magnitude than in clear cell ovarian carcinoma and endometrioid ovarian carcinoma across both cohorts. The benefit derived in low-grade serous ovarian carcinoma is also high (multivariable HR = 0.27 in Scottish cohort). Complete macroscopic resection was associated with prolonged survival in mucinous ovarian carcinoma patients in the SEER cohort (multivariable HR = 0.65), but the association failed to reach statistical significance in the Scottish cohort. Conclusions The overall ovarian cancer patient population demonstrates clinically significant survival benefit associated with complete macroscopic resection; however, the magnitude of benefit differs between histotypes.

The prognostic and predictive effect of body mass index in hormone receptor-positive breast cancer

Abstract Background Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients. Methods Patients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole after 2 to 3 years of adjuvant tamoxifen in postmenopausal women with HR+ BC. Patients were classified as normal weight (BMI: 18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obese (≥30.0 kg/m2). The primary endpoint was DFS, evaluated from randomization (prognostic analyses) or 3 years after randomization onwards (predictive analyses; aDFS) using multivariable Cox regression analyses. P-values were 2-sided. Results This study included 678 normal weight, 712 overweight, and 391 obese patients. After a median follow-up of 13.1 years, overweight and obesity were identified as negative prognostic factors for DFS (hazard ratio (HR) = 1.16; 95% confidence interval (CI) = 0.97 to 1.38 and HR = 1.26; 95% CI = 1.03 to 1.54, respectively). The adverse prognostic effect of BMI was observed in women aged younger than 60 years, but not in women aged 60 years or older (P-interaction = .009). The effect of extended anastrozole on aDFS was similar in normal weight (HR = 1.00; 95% CI = 0.74 to 1.35), overweight (HR = 0.74; 95% CI = 0.56 to 0.98), and obese patients (HR = 0.97; 95% CI = 0.69 to 1.36) (P-interaction = .24). Conclusion In this study among 1781 HR+ BC patients, overweight and obesity were adverse prognostic factors for DFS. BMI did not impact the efficacy of extended anastrozole.

Randomized trial promoting cancer genetic risk assessment when genetic counseling cost removed: 1-year follow-up

Abstract Purpose Cancer genetic risk assessment (CGRA) is recommended for women with ovarian and high-risk breast cancer. However, the underutilization of CGRA has long been documented, and cost has been a major barrier. In this randomized controlled trial, a tailored counseling and navigation (TCN) intervention significantly improved CGRA uptake at 6-month follow-up, compared with targeted print (TP) and usual care (UC). We aimed to examine the effect of removing genetic counseling costs on CGRA uptake by 12 months. Methods We recruited racially and geographically diverse women with breast and ovarian cancer from cancer registries in Colorado, New Jersey, and New Mexico. Participants assigned to TCN received telephone-based psychoeducation and navigation. After 6 months, the trial provided free genetic counseling to participants in all arms. Results At 12 months, more women in TCN obtained CGRA (26.6%) than those in TP (11.0%; odds ratio [OR] = 2.77, 95% confidence interval [CI] = 1.56 to 4.89) and UC (12.2%; OR = 2.46, 95% CI = 1.41 to 4.29). There were no significant differences in CGRA uptake between TP and UC. The Kaplan-Meier curve shows that the divergence of cumulative incidence slopes (TCN vs UC, TCN vs TP) appears primarily within the initial 6 months. Conclusion TCN significantly increased CGRA uptake at the 12-month follow-up. Directly removing the costs of genetic counseling attenuated the effects of TCN, highlighting the critical enabling role played by cost coverage. Future policies and interventions should address multilevel cost-related barriers to expand patients’ access to CGRA. Trial Registration This trial was registered with the NIH clinical trial registry, clinicaltrials.gov, NCT03326713. https://clinicaltrials.gov/ct2/show/NCT03326713.

Using clinical and genetic risk factors for risk prediction of 8 cancers in the UK Biobank

Abstract Background Models with polygenic risk scores and clinical factors to predict risk of different cancers have been developed, but these models have been limited by the polygenic risk score–derivation methods and the incomplete selection of clinical variables. Methods We used UK Biobank to train the best polygenic risk scores for 8 cancers (bladder, breast, colorectal, kidney, lung, ovarian, pancreatic, and prostate cancers) and select relevant clinical variables from 733 baseline traits through extreme gradient boosting (XGBoost). Combining polygenic risk scores and clinical variables, we developed Cox proportional hazards models for risk prediction in these cancers. Results Our models achieved high prediction accuracy for 8 cancers, with areas under the curve ranging from 0.618 (95% confidence interval = 0.581 to 0.655) for ovarian cancer to 0.831 (95% confidence interval = 0.817 to 0.845) for lung cancer. Additionally, our models could identify individuals at a high risk for developing cancer. For example, the risk of breast cancer for individuals in the top 5% score quantile was nearly 13 times greater than for individuals in the lowest 10%. Furthermore, we observed a higher proportion of individuals with high polygenic risk scores in the early-onset group but a higher proportion of individuals at high clinical risk in the late-onset group. Conclusion Our models demonstrated the potential to predict cancer risk and identify high-risk individuals with great generalizability to different cancers. Our findings suggested that the polygenic risk score model is more predictive for the cancer risk of early-onset patients than for late-onset patients, while the clinical risk model is more predictive for late-onset patients. Meanwhile, combining polygenic risk scores and clinical risk factors has overall better predictive performance than using polygenic risk scores or clinical risk factors alone.

Impact of chemotherapy on patients with mismatch repair deficient advanced endometrial carcinomas—a meta-analysis

Abstract Background Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient endometrial carcinoma. However, it is uncertain whether patients with mismatch repair deficient advanced or recurrent endometrial carcinoma derive less benefit from chemotherapy than those with mismatch repair proficient endometrial carcinoma. Methods We performed a meta-analysis of randomized controlled trials (RCTs) in advanced or recurrent endometrial carcinoma to determine the difference in the benefit of chemotherapy in mismatch repair deficient vs mismatch repair proficient endometrial carcinoma. Data on chemotherapy outcomes including objective response rate, progression-free survival (PFS), and overall survival were retrieved. We pooled these data using the inverse variance method and examined subgroup difference by mismatch repair status. We also compared differences in PFS and overall survival outcomes by creating individual patient data from the Kaplan–Meier curves of trial publications for sensitivity analyses. Results A total of 5 RCTs with 1137 participants (mismatch repair deficient, 26%; mismatch repair proficient, 74%) were included. All participants were treated with carboplatin-based chemotherapy. There was no difference between the mismatch repair deficient and mismatch repair proficient subgroups for objective response rate (66.5% vs 64.0%; P = .20 for subgroup difference), PFS (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.77 to 1.12; P = .44; median PFS = 7.6 vs 9.5 months) or overall survival (HR = 1.03, 95% CI = 0.73 to 1.44; P = .88; median overall survival = not reached vs 28.6 months). Conclusions Objective response rate, PFS, and overall survival were similar among those with mismatch repair deficient vs mismatch repair proficient endometrial cancer treated with front-line, platinum-doublet chemotherapy in RCTs. These findings reinforce the importance of combining chemotherapy together with immune checkpoint inhibitors until the results of trials comparing immune checkpoint therapy alone with combination therapy are available.

Physical Activity From Adolescence Through Midlife and Associations With Body Mass Index and Endometrial Cancer Risk

Abstract Background Physical activity is associated with lower risk for endometrial cancer, but the extent to which the association is mediated by body mass index (BMI) in midlife is unclear. This study describes the physical activity–endometrial cancer association and whether BMI mediates this relationship. Methods Participants were 67 705 women in the National Institutes of Health-AARP Diet and Health Study (50-71 years) who recalled their physical activity patterns starting at age 15-18 years. We identified 5 long-term physical activity patterns between adolescence and cohort entry (ie, inactive, maintained low, maintained high, increasers, decreasers). We used Cox regression to assess the relationship between these patterns and midlife BMI and endometrial cancer, adjusting for covariates. Mediation analysis was used to estimate the proportion of the physical activity–endometrial cancer association that was mediated by midlife BMI. Results During an average 12.4 years of follow-up 1468 endometrial cancers occurred. Compared with long-term inactive women, women who maintained high or increased activity levels had a 19% to 26% lower risk for endometrial cancer (maintained high activity: hazard ratio = 0.81, 95% confidence interval [CI] = 0.67 to 0.98; increasers: hazard ratio = 0.74, 95% CI = 0.61 to 0.91). They also had a 50% to 77% lower risk for obesity in midlife (eg, maintained high activity: odds ratio for a BMI of 30-39.9 kg/m2 = 0.50, 95% CI = 0.46 to 0.55; and maintained high activity, odds ratio for a BMI of ≥40 kg/m2 = 0.32, 95% CI = 0.26 to 0.39). BMI was a statistically significant mediator accounting for 55.5% to 62.7% of the physical activity–endometrial cancer associations observed. Conclusions Both maintaining physical activity throughout adulthood and adopting activity later in adulthood can play a role in preventing obesity and lowering the risk for endometrial cancer.

Quantifying the impact of introducing HPV vaccines in 2006 on 25-29-year-old cervical cancer incidence in 2022

Abstract Nearly all cervical cancers are caused by human papillomavirus (HPV). In 2006, adolescent females were recommended to receive the HPV vaccine. Our study aimed to quantify the impact of introducing the HPV vaccine in 2006 on cervical cancer incidence in 2022. We analyzed the latest Surveillance, Epidemiology, and End Results data. Our design compared the change in cervical cancer incidence from 2019 to 2022 between females recommended for HPV vaccination in 2006 (age 25-29) and females who were not (age 35-54). Beyond simple pre/post comparisons, our linear regression model adjusted for age-specific incidence trends. We found that, unlike the stagnate trends in older females between 2019 and 2022, in 25-29-year-old females, cervical cancer incidence declined 2.1 cases/100 000 (95% CI = −2.7 to −1.6): a 48% reduction from baseline trends. Although tempered by uneven adherence, after 15 years we finally appear to be realizing quantifiable benefits from this cancer prevention vaccine.

Germline reflex BRCA1/2 testing following tumor-only comprehensive genomic profiling: why, when, and how

Abstract The majority of tumor comprehensive genomic profiling (CGP) currently does not include a matched normal control. The use of a tumor-only CGP approach needs the development of a strategy to refine germline pathogenic/likely pathogenic variants (gP/LPVs) calls, so as to limit the performance of unnecessary germline reflex tests and instead successfully identify patients who are carriers of likely gP/LPVs. Guidelines have been developed for the identification of gP/LPVs in BRCA1/2 genes on the basis of tumor-only CGP results and for the evaluation of the appropriateness of performing germline reflex BRCA1/2 testing. In this study, an algorithm to assist decision-making for germline reflex testing of BRCA1/2 variants following tumor-only CGP is proposed.

The cervical cancer divide: state variation in incidence, mortality, and progress toward elimination in the United States

Abstract Cervical cancer elimination (<4 cases per 100 000) is a critical cancer prevention goal in the United States. Implementation of health policies and allocation of health resources occur at regional and state levels; therefore, understanding region- and state-specific cervical cancer incidence, mortality, and progress toward elimination—and remaining gaps—is essential. We estimated hysterectomy-corrected cervical cancer incidence, mortality, and progress toward elimination across all 50 states, the District of Columbia, and Puerto Rico. In 2021, Massachusetts was the only state nearing (4.3 per 100 000) the elimination threshold. Southeastern and Southwestern states were furthest, with the highest incidence rates in Mississippi (14.8), Louisiana (14.2), and Oklahoma (13.8). The mortality rate ranged from 6.8 (Alabama) to 1.4 (Wisconsin). In most states, cervical cancer incidence and mortality did not change from 2007-2011 to 2017-2021. Identifying and addressing regional- and state-level barriers impeding progress will be key to achieving cervical cancer elimination.

Magnitude of persistent poverty and cervical cancer incidence, stage at diagnosis, and mortality

Abstract Socioeconomically disadvantaged counties exhibit higher cervical cancer incidence and poorer survival. However, the specific impact of the magnitude of persistent poverty on these outcomes remains largely unexamined. Using national cancer registry data, we observed that women living in persistent poverty counties who have experienced extreme poverty (≥40% poverty) have more than 1.5 times higher cervical cancer incidence and twice the mortality rate as women who lived in nonpersistent poverty counties. Furthermore, stage-specific incidence was consistently higher in persistent poverty counties across localized, regional, and distant diagnoses. Five-year mortality for localized cervical cancer diagnoses was nearly twice as high in extreme poverty counties (11% vs 6%, 2-sided P = .03). These findings highlight substantial disparities in cervical cancer outcomes associated with increasing magnitude of persistent poverty and underscore the need for targeted interventions in economically vulnerable communities to reduce disparities and achieve cervical cancer elimination goals.

Improving real-world evaluation of patient- and physician-reported tolerability: niraparib for recurrent ovarian cancer (NiQoLe)

Abstract Background Maintenance niraparib at an individualized starting dose (ISD) is established in platinum-sensitive recurrent ovarian cancer (PSROC). However, patients’ perspectives on the burden of prolonged maintenance therapy have not been reported in prospective trials or routine practice. Methods In the real-life multicenter NiQoLe study, patients with PSROC received ISD maintenance niraparib. The primary objective was to describe physician-reported adverse events (AEs) leading to treatment modification during the first 3 months. Secondary endpoints included patient-reported outcomes (symptomatic AEs using PRO-CTCAE, self-reported fatigue, and impact on daily activities/function using FACT-F) collected remotely weekly using a specifically designed electronic device. Results Most (80%) of 139 treated patients (median age = 70 years) began niraparib at 200 mg/day. Median treatment duration was 5.7 (range = 0.2-21.4) months. During the first 3 months, 86 patients (62%) required treatment modification (median = 27 days to modification). Physician-reported grade ≥3 niraparib-related AEs occurred in 34 patients (24%); 68 patients (49%) had treatment modification for AEs, predominantly thrombocytopenia. The most frequent patient-reported AEs (PRO-CTCAE) were fatigue, insomnia, constipation, and dry mouth. Self-reported AEs were severe in 66% of patients. At baseline, 33% of patients reported severe fatigue (FACT-F), which generally persisted during niraparib. Physicians systematically underestimated major patient-reported symptoms. Conclusions In routine practice, niraparib dose modification was often required during the first 3 months despite individualized dosing. Physicians underestimated the burden of fatigue and symptomatic AEs. Digital self-reporting of AEs is feasible, provides patient-centered information complementing physician-reported AEs, and allows fuller appreciation of toxicity in real-world studies. Clinical trial information NCT03752216

Trends in Medicare payments within the first year of cervical cancer diagnosis, 2010-2019

Abstract Assessing Medicare payment trends for cervical cancer care is important to mitigate the financial impact on Medicare. This multiyear cross-sectional study included 65 years and older cervical cancer patients in SEER registries diagnosed between 2010 and 2019 who had continuous Part A and B Medicare coverage at least 6 months before diagnosis and at least within the first year of diagnosis and were not enrolled in any Health Maintenance Organization (HMO) in this duration. The main outcomes were trends in total and service-specific mean monthly Medicare payments within the first year of a cervical cancer diagnosis. This study included 2147 cervical cancer patients. The mean Medicare payments increased from $8300 in 2010 to $8520 in 2019, largely driven by a statistically significant increase in outpatient services costs, from $1361 to $2056 (AAPC = 5.45, 95% CI = 1.38 to 9.67, P = .008). These findings highlight the need for policy actions to mitigate cervical-cancer-related financial impact on Medicare.

Assessing impact of a community-based screening campaign to address social determinants of cervical cancer

Abstract Background Screening represents a cornerstone of cervical cancer control strategy. However, disparities in social determinants of health have perpetuated gaps in screening among racial and ethnic minorities. Social determinants of health including cultural stigma and lack of insurance have contributed to decreased screening among Hispanic women. To increase cancer screening in this population, community–academic partnerships and culturally tailored media have emerged as promising strategies. Methods This study assessed the impact of a culturally tailored cervical cancer screening campaign implemented through academic–community–government partnerships. Intercept surveys, conducted from 2015 to 2018 in eastern neighborhoods of Los Angeles, assessed campaign recall, interpretation, and screening intention among Hispanic women aged 21-65 years after exposure to the campaign. Screening intention was evaluated using χ2 and logistic regression by participant characteristics, with thematic analysis for campaign interpretation. Results Of 673 participants, 26.1% were uninsured, and 85.9% primarily spoke Spanish at home. Campaign recall was 25.1%, with 64.5% interpreting the campaign’s message as cervical cancer screening or health checkups. The campaign’s most liked aspect was emphasis on family (cited by 37.1% of participants). Postcampaign, 89.5% of participants overall were likely or extremely likely to schedule a Pap test, including 83.5% of women who had not had a Pap test in the past 3 years. Conclusions Our findings underscore several important strategies to reduce cervical cancer disparities: (1) associating positive cultural values with screening to decrease stigma, (2) combining culturally tailored outreach with interventions that target other known screening barriers, (3) facilitating long-term community relationships, and (4) leveraging academic–community–government partnerships.

Low CD86 expression is a predictive biomarker for clinical response to the therapeutic human papillomavirus vaccine IGMKK16E7: results of a post hoc analysis

Abstract Background Although therapeutic human papillomavirus vaccines could offer a noninvasive treatment for patients with cervical intraepithelial neoplasia, none has been clinically implemented. Oral administration of the therapeutic human papillomavirus vaccine IGMKK16E7 results in the histological regression of human papillomavirus 16–positive cervical intraepithelial neoplasia 2/3 to normal (complete response). We investigated biomarkers that could predict complete response after oral administration of IGMKK16E7. Methods Forty-two patients administered high-dose oral IGMKK16E7 in a phase I/II trial were included. Cervix-exfoliated cells were collected before vaccine administration. Gene expression of CD4, CD8, FOXP3, programmed cell death 1 protein, CTLA4, CD103, CD28, CD80, CD86, and programmed cell death 1 ligand 1 in the cells was measured by quantitative reverse transcriptase–polymerase chain reaction. Receiver operating characteristic curve analysis and Mann-Whitney tests were used to explore potential biomarkers. Pearson correlation coefficient analysis was used to correlate gene expression profiles with clinical outcome. Results The only predictive biomarker of vaccine response for which receiver operating characteristic curve analysis showed significant diagnostic performance with histological complete response was CD86 (area under the curve = 0.71, 95% confidence interval = 0.53 to 0.88, P = .020). Patients with complete response had significantly lower CD86 expression (CD86-low) than patients with no complete response (P = .035). The complete response rates for CD86-low and CD86-high patients were 50% and 19%, respectively, and CD86-low patients had a significantly higher complete response rate (P = .047). Compared with all patients, the CD86-low group had a 1.5-fold increase in the complete response rate. Gene expression of CD86 and CTLA4 showed the strongest positive correlation with clinical outcomes in the incomplete response group (P < .001). Conclusion Low expression of CD86 in exfoliated cervical cells can be used as a pretreatment biomarker to predict histological complete response after IGMKK16E7 administration.

Cultural shifts: an examination of cervical cancer stigma across age groups in the Caribbean

Abstract Background Cervical cancer-related stigma is common but understudied in the Caribbean. This study aims to describe the age difference of cervical cancer stigma and to evaluate the influence on the prevention practices among the Caribbean nonpatient population in Jamaica, Grenada, and Trinidad and Tobago. Methods A cross-sectional study involving 1209 participants was conducted using a culturally trans-created Cancer Stigma Scale for the Caribbean context and supplemented with questions on cervical cancer and human papillomavirus (HPV) and HPV vaccine knowledge and beliefs. Descriptive analyses and χ2 tests were conducted. Results The χ2 tests showed age is statistically significantly related to participants’ response to stigma items such as “community members believe cervical cancer is viewed as shameful” (P = .0001); “women with cervical cancer are treated with less respect than usual by others” (P < .0001); “women with cervical cancer are rejected by family members” (P = .0007); “women with cervical cancer are rejected by intimate partners” (P < .0001); and “intimate partners blame women for having cervical cancer” (P = .0032). Additionally, age has statistically significant associations with endorsements of negative views of cervical cancer from the community (P < .0001) and family (P < .0001) as key barriers to cervical cancer care (item: “discourage women from seeking and obtaining screening and treatment”). Notably, younger respondents (18-25 years) are more sensitized to the unfair stigma and hold more stigma. Conclusions Among Caribbeans, age influences cervical cancer stigma. Younger persons acknowledged greater stigma within families and communities. This study can guide age-informed interventions and programs to reduce stigma and improve cervical cancer screening and care seeking to reduce cervical cancer burden and disparities.

Cervical cancer treatment outcomes and survival in Botswana by human immunodeficiency virus status: Ipabalele study results

Abstract Background Cervical cancer is a leading morbidity/mortality cause, frequently co-occurring with human immunodeficiency virus (HIV) positivity, in Botswana. We examined long-term outcomes for Ipabalele study participants receiving curative chemoradiation for locally advanced cervical cancer (2015-2019) by HIV status. Methods Clinical and outcome data were collected at baseline, treatment completion, and 3 months thereafter. Patients were followed for up to 5 years. Overall survival (OS) was evaluated using Kaplan-Meier curves and Cox regression. Results The cohort comprised 295 patients (73.8% with HIV, younger at diagnosis [P < .001]) followed for a median of 44.2 months. Complete response was seen in 217/278 (76.1%) patients. Two- and 5-year OS rates were 73.4% and 59.9%, respectively, with no difference by HIV status. OS was associated negatively with advanced disease stage (III: hazard ratio [HR] 13.23, P < .001; IV: HR 7.8, P = .008) and positively with increased radiation (HR 0.977, P = .0005) and chemotherapy (HR 0.85, P = .005). Clinical response was associated negatively with advanced disease (IV: HR 0.113, P = .002) and positively with increased radiation (P = .009). Toxicity did not differ by HIV status. The most common grade-≥-2 non-hematological and hematological toxicities were radiation dermatitis (39.8%) and reduced white blood cell count (66.05%), respectively. Conclusions In this cervical cancer cohort with good HIV status control, treatment outcomes and OS were associated with disease and treatment factors, not the HIV status. Early screening and education regarding treatment protocols are crucial to improve cervical cancer outcomes in Botswana.

Weight Change and Incident Distal Colorectal Adenoma Risk in the PLCO Cancer Screening Trial

Abstract Background Although obesity is a known risk factor, the impact of weight change on colorectal adenoma risk is less clear and could have important implications in disease prevention. We prospectively evaluated weight change in adulthood and incident colorectal adenoma. Methods We assessed weight change during early-late (age 20 years to baseline, ie, ages 55-74 years), early-middle (20-50 years), and middle-late (50 years-baseline) adulthood using self-reported weight data in relation to incident distal adenoma in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (cases = 1053; controls = 16 576). For each period, we defined stable weight as greater than −0.5 kg to less than or equal to 1 kg/5 years, weight loss as less than or equal to −0.5 kg/5 years, and weight gain as greater than 1-2, greater than 2-3, or greater than 3 kg/5 years. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression; all tests were 2-sided. Results Compared with stable weight, weight loss during early-late adulthood was associated with reduced adenoma risk (OR = 0.54, 95% CI = 0.34 to 0.86), particularly among those who were overweight or obese at age 20 years (OR = 0.39, 95% CI = 0.18 to 0.84). Results were similar for early-middle adulthood but less pronounced for middle-late adulthood. Weight gain greater than 3 kg/5 years during early-late adulthood was associated with increased risk (OR = 1.30, 95% CI = 1.07 to 1.58, Ptrend < .001). Findings appeared stronger among men (OR for >3 kg/5 years = 1.41, 95% CI = 1.11 to 1.80) than women (OR = 1.09, 95% CI = 0.79 to 1.50, Pinteraction = .21). Conclusions Weight loss in adulthood was associated with reduced adenoma risk, particularly for those who were overweight or obese, whereas weight gain greater than 3 kg/5 years increased risk. Findings underscore the importance of healthy weight maintenance throughout adulthood in preventing colorectal adenoma.

Improving Cervical Precancer Surveillance: Validity of Claims-Based Prediction Models in ICD-9 and ICD-10 Eras

AbstractBackgroundHuman papillomavirus vaccine (HPV) impact on cervical precancer (cervical intraepithelial neoplasia grades 2+ [CIN2+]) is observable sooner than impact on cancer. Biopsy-confirmed CIN2+ is not included in most US cancer registries. Billing codes could provide surrogate metrics; however, the International Classification of Diseases, ninth (ICD-9) to tenth (ICD-10) transition disrupts trends. We built, validated, and compared claims-based models to identify CIN2+ events in both ICD eras.MethodsA database of Davidson County (Nashville), Tennessee, pathology-confirmed CIN2+ from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT) provided gold standard events. Using Tennessee Medicaid 2008-2017, cervical diagnostic procedures (N = 8549) among Davidson County women aged 18-39 years were randomly split into 60% training and 40% testing sets. Relevant diagnosis, procedure, and screening codes were used to build models from CIN2+ tissue diagnosis codes alone, least absolute shrinkage and selection operator (LASSO), and random forest. Model-classified index events were counted to estimate incident events.ResultsHPV-IMPACT identified 983 incident CIN2+ events. Models identified 1007 (LASSO), 1245 (CIN2+ tissue diagnosis codes alone), and 957 (random forest) incident events. LASSO performed well in ICD-9 and ICD-10 eras: 77.3% (95% confidence interval [CI] = 72.5% to 81.5%) vs 81.1% (95% CI = 71.5% to 88.6%) sensitivity, 93.0% (95% CI = 91.9% to 94.0%) vs 90.2% (95% CI = 87.2% to 92.7%) specificity, 61.3% (95% CI = 56.6% to 65.8%) vs 60.3% (95% CI = 51.0% to 69.1%) positive predictive value, 96.6% (95% CI = 95.8% to 97.3%) vs 96.3% (95% CI = 94.1% to 97.8%) negative predictive value, 91.0% (95% CI = 89.9% to 92.1%) vs 88.8% (95% CI = 85.9% to 91.2%) accuracy, and 85.1% (95% CI = 82.9% to 87.4%) vs 85.6% (95% CI = 81.4% to 89.9%) C-indices, respectively; performance did not statistically significantly differ between eras (95% confidence intervals all overlapped).ConclusionsResults confirmed model utility with good performance across both ICD eras for CIN2+ surveillance. Validated claims-based models may be used in future CIN2+ trend analyses to estimate HPV vaccine impact where population-based biopsies are unavailable.

Differential trends in rising endometrial cancer incidence by age, race, and ethnicity

Abstract Endometrial cancer (EC) incidence is on the rise. Although early-onset endometrial cancer (EOEC; age at diagnosis <50 years) is relatively uncommon, the incidence of EOEC has been reportedly increasing in recent decades. However, the rising EOEC has not been thoroughly described with regard to the racial and ethnic disparities and compared with late-onset EC (age at diagnosis ≥50 years). We used the Cancer in North America (CiNA) Analytic File, 1995-2018, from the North American Association of Central Cancer Registries, which allowed us to examine trends in invasive EC incidence by racial and ethnic groups and by age at diagnosis. We found striking differences for demographic and tumor characteristics as well as racial and ethnic patterns and time trends in EC incidence between EOEC and late-onset EC. The faster increases in EOEC incidence rates, especially among non-White women, mirror similar observations in other cancers, pointing to a possible link with rising obesity epidemic in younger generations.

Neighborhood-level social determinants of health burden among adolescent and young adult cancer patients and impact on overall survival

Abstract Background Neighborhood socioeconomic deprivation has been linked to adverse health outcomes, yet it is unclear whether neighborhood-level social determinants of health (SDOH) measures affect overall survival in adolescent and young adult patients with cancer. Methods This study used a diverse cohort of adolescent and young adult patients with cancer (N = 10 261) seen at MD Anderson Cancer Center. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI values representing worse SDOH. Results ADI was statistically significantly worse (P < .050) for Black (61.7) and Hispanic (65.3) patients than for White patients (51.2). Analysis of ADI by cancer type showed statistically significant differences, mainly driven by worse ADI in patients with cervical cancer (62.3) than with other cancers. In multivariable models including sex, age at diagnosis, cancer diagnosis, and race and ethnicity, risk of shorter survival for people residing in neighborhoods with the least favorable ADI quartile was greater than for individuals in the most favorable ADI quartile (hazard ratio = 1.09, 95% confidence interval = 1.00 to 1.19, P = .043). Conclusion Adolescent and young adult patients with cancer and the worst ADI values experienced a nearly 10% increase in risk of dying than patients with more favorable ADI values. This effect was strongest among White adolescent and young adult survivors. Although the magnitude of the effect of ADI on survival was moderate, the presence of a relationship between neighborhood-level SDOH and survival among patients who received care at a tertiary cancer center suggests that ADI is a meaningful predictor of survival. These findings provide intriguing evidence for potential interventions aimed at supporting adolescent and young adult patients with cancer from disadvantaged neighborhoods.

Patterns and trends in the cause of death for patients with endometrial cancer

AbstractBackgroundRacial disparities in endometrial cancer have been reported in the United States, but trends and the underlying causes are not well understood. We aimed to examine the trends and contributing factors in racial disparities for causes of death among endometrial cancer patients.MethodIn this population-based cohort study, we identified 139 473 women diagnosed with first, primary endometrial cancer between 1992 to 2018 from the Surveillance, Epidemiology, and End Results Program. We used the “Fine and Gray” method to calculate the cumulative incidence of all-cause and specific-cause death. We used proportional subdistribution hazard (PSH) and cause-specific hazard (CSH) models to quantify the relative risk of Black–White disparities. We performed a mediation analysis to assess the contribution of potential factors to disparities.ResultsThe cumulative incidence of all-cause death decreased in endometrial cancer patients, with estimates at 5 years of 26.72% in 1992-1996 and 22.59% in 2007-2011. Compared with White patients, Black patients persistently had an increased risk of death due to endometrial cancer (PSH hazard ratio [HR] = 2.05, 95% confidence interval [CI] = 1.90 to 2.22; CSH HR = 2.19, 95% CI = 2.00 to 2.40) and causes other than endometrial cancer (PSH HR = 1.23, 95% CI = 1.10 to 1.37; CSH HR = 1.46, 95% CI = 1.31 to 1.63). Grade, histological subtype, surgery utilization, and stage at diagnosis explained 24.4%, 20.1%, 18.4%, and 16.6% of the Black-White disparity in all-cause death, respectively.ConclusionsAlthough the cumulative incidence of all-cause death decreased, the Black–White gaps persisted in patients with endometrial cancer. Grade and histological subtype had the greatest influence. More efforts are needed to address the disparities.

Association Between Adrenal-Restrictive HSD3B1 Inheritance and Hormone-Independent Subtypes of Endometrial and Breast Cancer

Abstract Background The germline variant rs1047303 (HSD3B1[1245A/C]), restricting or enabling production of potent androgens and estrogens from adrenal precursors, affects outcomes of castration-resistant prostate cancer and is associated with estrogen receptor positivity in postmenopausal breast cancer. Like breast cancer, endometrial cancer is another malignancy with hormone-dependent and hormone-independent subtypes. We hypothesized that adrenal-restrictive HSD3B1 genotype would associate with hormone-independent cancer subtypes. Methods We employed a previously described classification of tumors in The Cancer Genome Atlas into genomic clusters. We determined HSD3B1 genotype frequencies by endometrial cancer genomic cluster and calculated the odds per adrenal-restrictive A allele for the largely hormone-independent copy-number (CN) high subtype vs other subtypes. An equivalent analysis was performed for the genomically similar, hormone-independent basal breast cancer subtype. Last, we performed survival analyses for UK Biobank participants with endometrial cancer by HSD3B1 genotype. All statistical tests were 2-sided. Results The adrenal-restrictive HSD3B1(1245A) allele was associated with the CN-high endometrial cancer subtype (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.14 to 2.32; P = .007). Similarly, HSD3B1(1245A) was associated with the basal breast cancer subtype (OR = 1.54, 95% CI = 1.13 to 2.08; P = .006). In the UK Biobank, endometrial cancer patients homozygous for HSD3B1(1245A) had worse overall (hazard ratio [HR] = 1.39, 95% CI = 1.16 to 1.68; P < .001) and cancer-specific (HR = 1.39, 95% CI = 1.14 to 1.70; P = .001) survival, consistent with the A allele being enriched in the more aggressive CN-high subtype. Conclusions These findings suggest roles for adrenal-restrictive vs adrenal-permissive steroidogenesis, by way of rs1047303 genotype, in the development of and/or outcomes from at least 3 commonly hormone-associated types of cancer: prostate, breast, and endometrial.

Socioeconomic determinants of cancer screening adherence among cancer survivors: analysis from the 2020 Behavioral Risk Factor Surveillance System

Abstract Background Factors associated with cancer survivors’ preventive health behaviors are understudied. We hypothesized that socioeconomic and health-care access factors may be associated with adherence to recommended cancer screenings. Methods We conducted a cross-sectional analysis using the 2020 Behavioral Risk Factor Surveillance System. Cancer survivors eligible for United States Preventive Services Task Force–recommended breast, cervical, prostate, and colorectal screenings were included. Multivariable logistic regression models were used to identify socioeconomic factors significantly associated with screening adherence. Results Overall, 64 958 (weighted national estimate = 29 066 143) cancer survivors were included. Adherence rates varied across cancer types: 80.9% for breast, 88.9% for cervical, 54.1% for prostate, and 84.7% for colorectal cancer. Key predictors of low adherence included lower income (breast: adjusted odds ratio [aOR] = 0.56, 95% confidence interval [CI] = 0.43 to 0.74; cervical: aOR = 0.38, 95% CI = 0.24 to 0.59; prostate: aOR = 0.36, 95% CI = 0.24 to 0.52; colorectal: aOR = 0.74, 95% CI = 0.57 to 0.96), lack of health-care coverage for colorectal cancer (aOR = 0.51, 95% CI = 0.36 to 0.73), time since last checkup between 1 and 2 years prior for breast (aOR = 0.58, 95% CI = 0.45 to 0.75), prostate (aOR = 0.66, 95% CI = 0.47 to 0.91), and colorectal (aOR = 0.69, 95% CI = 0.56 to 0.86) cancer, and no health-care provider for breast (aOR = 0.68, 95% CI = 0.47 to 0.98), prostate (aOR = 0.45, 95% CI = 0.31 to 0.65), and colorectal (aOR = 0.51, 95% CI = 0.40 to 0.66) cancer. Conclusion Cancer survivors’ adherence to screening is associated with factors including lack of health-care coverage, lower income, time since the last exam, and having a personal provider. Targeted interventions accounting for such factors may help mitigate these disparities.

Health-care access dimensions and ovarian cancer survival: SEER-Medicare analysis of the ORCHiD study

AbstractBackgroundRacial and ethnic disparities in ovarian cancer (OC) survival are well-documented. However, few studies have investigated how health-care access (HCA) contributes to these disparities.MethodsTo evaluate the influence of HCA on OC mortality, we analyzed 2008-2015 Surveillance, Epidemiology, and End Results-Medicare data. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HCA dimensions (affordability, availability, accessibility) and OC-specific and all-cause mortality, adjusting for patient characteristics and treatment receipt.ResultsThe study cohort included 7590 OC patients: 454 (6.0%) Hispanic, 501 (6.6%) Non-Hispanic (NH) Black, and 6635 (87.4%) NH White. Higher affordability (HR = 0.90, 95% CI = 0.87 to 0.94), availability (HR = 0.95, 95% CI = 0.92 to 0.99), and accessibility scores (HR = 0.93, 95% CI = 0.87 to 0.99) were associated with lower risk of OC mortality after adjusting for demographic and clinical factors. Racial disparities were observed after additional adjustment for these HCA dimensions: NH Black patients experienced a 26% higher risk of OC mortality compared with NH White patients (HR = 1.26, 95% CI = 1.11 to 1.43) and a 45% higher risk among patients who survived at least 12 months (HR = 1.45, 95% CI = 1.16 to 1.81).ConclusionsHCA dimensions are statistically significantly associated with mortality after OC and explain some, but not all, of the observed racial disparity in survival of patients with OC. Although equalizing access to quality health care remains critical, research on other HCA dimensions is needed to determine additional factors contributing to disparate OC outcomes by race and ethnicity and advance the field toward health equity.

Phase I and II randomized clinical trial of an oral therapeutic vaccine targeting human papillomavirus for treatment of cervical intraepithelial neoplasia 2 and 3

Abstract Background Although many human papillomavirus (HPV)–targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus-based oral vaccine. Methods In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16–positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. Results In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P = .83). The number of HPV-16 E7–specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner. Conclusion This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16–positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects. Trial registration jRCT2031190034.

Motivators of Inappropriate Ovarian Cancer Screening: A Survey of Women and Their Clinicians

Abstract Background This study examined why women and doctors screen for ovarian cancer (OC) contrary to guidelines. Methods Surveys, based on the Theoretical Domains Framework, were sent to women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer and family physicians and gynecologists who organized their screening. Results Of 1264 Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer women, 832 (65.8%) responded. In the past 2 years, 126 (15.1%) had screened. Most of these (n = 101, 80.2%) would continue even if their doctor told them it is ineffective. For women, key OC screening motivators operated in the domains of social role and goals (staying healthy for family, 93.9%), emotion and reinforcement (peace of mind, 93.1%), and beliefs about capabilities (tests are easy to have, 91.9%). Of 531 clinicians 252 (47.5%) responded; a minority (family physicians 45.8%, gynecologists 16.7%) thought OC screening was useful. For gynecologists, the main motivators of OC screening operated in the domains of environmental context (lack of other screening options, 27.6%), and emotion (patient peace of mind, 17.2%; difficulty discontinuing screening, 13.8%). For family physicians,, the strongest motivators were in the domains of social influence (women ask for these tests, 20.7%), goals (a chance these tests will detect cancer early, 16.4%), emotion (patient peace of mind, 13.8%), and environmental context (no other OC screening options, 11.2%). Conclusion Reasons for OC screening are mostly patient driven. Clinician knowledge and practice are discordant. Motivators of OC screening encompass several domains, which could be targeted in interventions to reduce inappropriate OC screening.

Salpingectomy for ectopic pregnancy reduces ovarian cancer risk—a nationwide study

Abstract Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316 882 women with surgical treatment for ectopic pregnancy and 3 168 820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.

Site-specific patterns of early-stage cancer diagnosis during the COVID-19 pandemic

Abstract The COVID-19 pandemic caused widespread disruptions in cancer care. We hypothesized that the greatest disruptions in diagnosis occurred in screen-detected cancers. We identified patients (≥18 years of age) with newly diagnosed cancer from 2019 to 2020 in the US National Cancer Database and calculated the change in proportion of early-stage to late-stage cancers using a weighted linear regression. Disruptions in early-stage diagnosis were greater than in late-stage diagnosis (17% vs 12.5%). Melanoma demonstrated the greatest relative decrease in early-stage vs late-stage diagnosis (22.9% vs 9.2%), whereas the decrease was similar for pancreatic cancer. Compared with breast cancer, cervical, melanoma, prostate, colorectal, and lung cancers showed the greatest disruptions in early-stage diagnosis. Uninsured patients experienced greater disruptions than privately insured patients. Disruptions in cancer diagnosis in 2020 had a larger impact on early-stage disease, particularly screen-detected cancers. Our study supports emerging evidence that primary care visits may play a critical role in early melanoma detection.

Social risk factors and cancer prevention care among patients in community health-care settings

Abstract Background Social risks are negatively associated with receipt of cancer preventive care. As knowledge is lacking on the pathways underlying these associations, we investigated associations between patient-reported social risks and colorectal cancer (CRC), cervical cancer, and breast cancer screening order provision and screening completion. Methods This study included patients eligible for CRC, cervical cancer, or breast cancer screening at 186 community-based clinics between July 1, 2015, and February 29, 2020. Outcomes included up-to-date status for indicated cancer screenings at baseline; percentage of subsequent study months in which patients were up-to-date on screenings; screening order receipt; and screening completion. Independent variables were patient-reported food insecurity, transportation barriers, and housing instability. Analyses used covariate-adjusted generalized estimating equation models, stratified by social risk. Results Patients with documented social risks were less likely to be up-to-date on any cancer screening at baseline and in most cases had a lower rate of total study months up-to-date on screenings. All cancer screenings were ordered less often for food-insecure patients. Cervical cancer screening was ordered less often for transportation-insecure patients. The likelihood of completing a screening test differed statistically significantly by select social risks: Cervical cancer and CRC screening rates were lower among food-insecure patients, and CRC screening rates were lower among transportation-insecure patients. The likelihood of breast cancer screening completion did not differ by social risk status. Conclusion Social risks affect both the ordering and the receipt of cancer screening. Research is needed on strategies to mitigate the impact of different social risks on cancer early-detection services.

Rural-urban disparities and trends in cancer screening: an analysis of Behavioral Risk Factor Surveillance System data (2018-2022)

Abstract Background Despite evidence of the benefit of routine cancer screenings, data show a concerning decline in cancer screening uptake for multiple cancers. This analysis aimed to examine rural-urban differences in recent trends for being up-to-date with screenings for breast, cervical, and colorectal cancers. Methods We used 2018, 2020, and 2022 Behavioral Risk Factor Surveillance System data to assess up-to-date cancer screening status among eligible adults in the United States. We calculated weighted prevalence estimates overall and stratified by county-level rural-urban classification. We used survey-weighted multivariable logistic regression models to examine rural-urban disparities in cancer screening up-to-date status by year. Results Prevalence of being up-to-date with each cancer screening was lower in 2022 than it was in 2018. The largest decline in screening overall was for cervical cancer, which dropped from 81.89% in 2018 to 47.71% in 2022. Rural-urban disparities were observed for breast cancer screening from 2018 to 2022, with the odds of up-to-date screening being 14% to 27% lower for rural populations than for urban populations. For colorectal and cervical cancers, the odds of being up-to-date with screenings were lower for rural populations in 2018 and 2020, but no statistically significant difference was observed in 2022 (colorectal screening odds ratio = 0.96, 95% CI = 0.90 to 1.02; cervical screening odds ratio = 0.97, 95% CI = 0.93 to 1.03). Conclusion There is a concerning trend of decreasing uptake of cancer screenings that will challenge future efforts in cancer prevention and control. There is a need to better understand the factors contributing to the decline in cancer screening update.

Self-sampling tools to increase cancer screening among underserved patients: a pilot randomized controlled trial

Abstract Background Screening can reduce cancer mortality, but uptake is suboptimal and characterized by disparities. Home-based self-sampling can facilitate screening for colorectal cancer (with stool tests, eg, fecal immunochemical tests) and for cervical cancer (with self-collected human papillomavirus tests), especially among patients who face barriers to accessing health care. Additional data are needed on feasibility and potential effects of self-sampling tools for cancer screening among underserved patients. Methods We conducted a pilot randomized controlled trial with patients (female, ages 50-65 years, out of date with colorectal and cervical cancer screening) recruited from federally qualified health centers in rural and racially segregated counties in Pennsylvania. Participants in the standard-of-care arm (n = 24) received screening reminder letters. Participants in the self-sampling arm (n = 24) received self-sampling tools for fecal immunochemical tests and human papillomavirus testing. We assessed uptake of screening (10-week follow-up), self-sampling screening outcomes, and psychosocial variables. Analyses used Fisher exact tests to assess the effect of study arm on outcomes. Results Cancer screening was higher in the self-sampling arm than the standard-of-care arm (colorectal: 75% vs 13%, respectively, odds ratio = 31.32, 95% confidence interval = 5.20 to 289.33; cervical: 79% vs 8%, odds ratio = 72.03, 95% confidence interval = 9.15 to 1141.41). Among participants who returned the self-sampling tools, the prevalence of abnormal findings was 24% for colorectal and 18% for cervical cancer screening. Cancer screening knowledge was positively associated with uptake (P < .05). Conclusions Self-sampling tools can increase colorectal and cervical cancer screening among unscreened, underserved patients. Increasing the use of self-sampling tools can improve primary care and cancer detection among underserved patients. Clinical Trials Registration Number STUDY00015480.

Spatial-Temporal Trends in Ovarian Cancer Outcomes in California

Abstract Background Research suggests that geographic location may affect ovarian cancer (OC) outcomes. Insurance status often remains an important predictor of outcomes. The Affordable Care Act was enacted in 2010 to expand access to affordable health insurance. Our objective was to examine spatiotemporal trends in OC treatment nonadherence and disease-specific mortality in California (USA) among women diagnosed with OC. Methods Newly diagnosed epithelial OC cases between 1996 and 2017 were identified from the California Cancer Registry. Spatiotemporal trends in adherence to treatment guidelines were examined using generalized additive models and OC-specific mortality using Cox proportional hazards additive models. Prediction grids covering California were used to display the odds ratios (ORs) and hazard ratios of location using the median value for the study area as the referent value. Seven overlapping 5-year periods and 2 larger ones (pre- and post-2013) were assessed. Analyses were stratified according to stage (early vs advanced) and used P = .05 to determine statistical significance. Results Statistically significant spatial patterns in treatment nonadherence were observed for every time period examined (P < .001). Odds of treatment nonadherence associated with geographic location were highest among women with early-stage OC in southern Los Angeles County during 2014-2017 (OR max = 3.89, confidence interval = 1.04 to 7.61). For women with advanced-stage OC, residing in northern California was generally associated with lower odds ratios, whereas southern California was associated with higher odds ratios, with higher odds in the latter time period (OR range = 0.53-1.84 in 1996-2012 vs 0.49-2.37 in 2013-2017). Geographic location was not a statistically significant predictor of mortality. Conclusions Residential location was statistically significantly associated with treatment received in California, with spatial patterns varying over time but not OC-specific mortality. Changes in insurance status over time were accompanied by shifts in population demographics and increased travel distances to receive care.

Trends in the Incidence of Human Papillomavirus-Associated Cancers by County-Level Income and Smoking Prevalence in the United States, 2000-2018

Abstract Human papillomavirus (HPV)-associated cancer burden is rising in the United States. Trends in the incidence by county-level income and smoking prevalence remain undescribed. We used the Surveillance, Epidemiology, and End Results 21 database to ascertain HPV-associated cancers during 2000-2018. Trends were estimated by county-level income and smoking prevalence quartiles. Anal and vulvar cancer incidence among women and anal cancer incidence among men increased markedly in the lowest-income counties, whereas the increases were slower in the highest-income counties (eg, for vulvar cancer, incidence increased 1.9% per year, 95% confidence interval [CI] = 0.9% to 2.9%, in the lowest-income counties vs 0.8% per year, 95% CI = 0.6% to 1.1%, in the highest-income counties). In recent years, cervical cancer incidence plateaued (0.0% per year [95% CI = −0.5% to 0.5%]) in the highest-income counties; in the lowest-income counties, the annual percentage change was 1.6% per year (95% CI = −0.7% to 4.0%). Counties with high smoking prevalence had marked increases in incidence compared with their counterparts (eg, anal cancer among men increased 4.4% per year [95% CI = 2.7% to 6.0%] for those living in counties with the highest smoking prevalence vs 1.2% per year [95% CI = 0.7% to 1.7%] for those living in counties with the lowest smoking prevalence). Improved and targeted prevention is needed to combat the widening disparities.

Human Papillomavirus Vaccination After COVID-19

Abstract The current global novel coronavirus disease 2019 (COVID-19) pandemic threatens to derail the uptake of human papillomavirus (HPV) vaccination in low- and lower-middle income countries with major disruptions to routine immunization and the introduction of new vaccines delayed. This has a major impact on the World Health Organization cervical cancer elimination strategy, where it is dependent on HPV vaccination as well as cervical cancer screening and treatment. We discuss current opportunities and barriers to achieve high uptake of HPV vaccination in low- and lower-middle income countries as well as the impact of COVID-19. Implementation of 4 key recommendations for HPV vaccination in low- and lower-middle income countries is needed: increased global financial investment; improved vaccine supply and accelerated use of a single-dose schedule; education and social marketing; and adoption of universal school-based delivery. With the commitment of the global health community, the adoption of these strategies would underpin the effective elimination of cervical cancer.

Body mass index and chemotherapy completion among patients with newly diagnosed ovarian cancer

Abstract Background Several ovarian cancer studies have suggested that a body mass index (BMI) of 30 or higher is associated with lower compliance with National Comprehensive Cancer Network–recommended chemotherapy but primarily involved treatment before 2012, when dose capping was recommended for patients with higher body surface areas. Updated analyses in the contemporary treatment era are warranted. Methods In a retrospective cohort of patients with newly diagnosed ovarian cancer receiving curative-intent carboplatin plus paclitaxel in the Yale-Smilow Cancer Network (2012-2022), we evaluated BMI at diagnosis in relation to relative dose intensity (RDI)—the ratio of completed chemotherapy dose intensity to the National Comprehensive Cancer Network–recommended dose intensity—which reflects dose modification both before and during treatment. We also assessed starting RDI (which reflects modifications before treatment) and received RDI (which reflects modifications during treatment). Data on hospitalizations and hematological chemotoxicities were collected. We examined the association between BMI (<25, 25-30, ≥30) and chemotherapy completion, hospitalizations, and toxicities using multivariable linear and logistic regressions. Results Among 327 patients, the average RDI was 79.7%, and 44.3% had an RDI below 85%. Mean (SD) starting and received RDI were 97.9% (9.1%) and 81.8% (25.7%), respectively. Higher BMI was associated with higher RDI (Paggregate = .03) and received RDI (Paggregate = .04). Body mass index was not associated with starting RDI, dose reductions, delays, hospitalizations, or hematological toxicities. Conclusions Among patients with ovarian cancer treated since 2012, the overall RDI was low. Relative dose intensity was higher among patients with a BMI of 25 or higher compared with a BMI below 25. Most dose modifications occurred during treatment and not before initiation. Studies with body composition data and interventions that maximize chemotherapy completion during treatment are warranted.