The Genomic Landscape of Vulvar Squamous Cell Carcinoma.

Vulvar squamous cell cancer (VSC) accounts for 90% of vulvar cancers. Next-generation sequencing studies of VSC imply human papillomavirus (HPV) and p53 status play separate roles in carcinogenesis and prognosis. We sought to describe the genomic landscape and analyze the immunologic profiles of VSC with respect to HPV and p53 status. A total of 443 VSC tumors underwent tumor profiling. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor samples. PD-L1, microsatellite instability were tested by fragment analysis, IHC, and next-generation sequencing. Tumor mutational burden-high was defined as >10 mutations per MB. HPV 16/18 positive (HPV+) status was determined using whole exome sequencing on 105 samples. Three cohorts were identified from 105 samples with known HPV: HPV+, HPV-/p53wt, and HPV-/p53mt. Where HPV and p53 status were examined, TP53 mutations were exclusive of HPV+ tumors. In all, 37% of samples were HPV+. Among the 66 HPV- tumors, 52 (78.8%) were HPV-/p53mt and 14 (21.2%) were HPV-/p53wt. The HPV-/p53wt cohort had a higher rate of mutations in the PI3KCA gene (42.9% HPV-/p53wt vs 26.3% HPV+ vs. 5.8% HPV-/p53mt, q =0.028) and alterations in the PI3K/AkT/mTOR pathway (57.1% HPV-/p53wt vs. 34.2% HPV+ vs. 7.7% HPV-/p53mt, q =0.0386) than the other 2 cohorts. Ninety-eight VSC tumors with HPV16/18 information underwent transcriptomic analysis and immune deconvolution method. No differences were observed in immune profiles. The HPV-/p53wt VSC tumors had significantly higher rates of mutations in the PI3KCA gene and alterations in the PI3K/AkT/mTOR pathway, a potential target that merits further investigation in this subgroup.

Concurrent Surgery for Locoregional Gynecologic Cancers and Pelvic Floor Disorders in a Population of Patients With Medicare Insurance.

OBJECTIVE: To estimate the rate of concurrent surgery for locoregional gynecologic cancer and pelvic organ prolapse-urinary incontinence (POP-UI) and to assess the rate of surgery for POP-UI within 5 years for those who did not undergo concurrent surgery. METHODS: This is a retrospective cohort study. The SEER-Medicare data set was used to identify cases of local or regional endometrial, cervical, and ovarian cancer diagnosed from 2000 to 2017. Patients were followed up for 5 years from diagnosis. We used χ 2 tests to identify categorical variables associated with having a concurrent POP-UI procedure with hysterectomy or within 5 years of hysterectomy. Logistic regression was used to calculate odds ratios and 95% CIs adjusted for variables statistically significant (α=.05) in the univariate analyses. RESULTS: Of 30,862 patients with locoregional gynecologic cancer, only 5.5% underwent concurrent POP-UI surgery. Of those with a preexisting diagnosis related to POP-UI, however, 21.1% had concurrent surgery. Of the patients who had a diagnosis of POP-UI at the time of initial surgery for cancer and who did not undergo concurrent surgery, an additional 5.5% had a second surgery for POP-UI within 5 years. The rate of concurrent surgery remained constant over the time period (5.7% in 2000 and 2017) despite an increase in the frequency of POP-UI diagnosis in the same time frame. CONCLUSION: The rate of concurrent surgery for patients with an early-stage gynecologic cancer and POP-UI-associated diagnosis in women older than age 65 years was 21.1%. Of women who did not undergo concurrent surgery but had a diagnosis of POP-UI, 1 in 18 underwent surgery for POP-UI within 5 years of their index cancer surgery. Dedicated efforts must be made to identify patients who would most benefit from concurrent cancer and POP-UI surgery in those with locoregional gynecologic cancers and pelvic floor disorders.

Incidence and Survival of Multiple Primary Cancers in US Women With a Gynecologic Cancer.

Objectives: To evaluate risk of a second cancer and associated survival times in United States women with diagnosis of cancer. Methods: The Surveillance Epidemiology and End Results (SEER) database was queried for 2 cohorts of women aged 18 - 89 with either an index gynecologic or non-gynecologic cancer diagnosed between 1992 - 2017. Index cases were followed to determine if a second primary cancer was subsequently diagnosed; defined according to SEER multiple primary and histology coding rules. Standard Incident Ratios (SIR) and latency intervals between index diagnosis and second primary diagnosis were evaluated. Among those who developed a second primary cancer, median survival times from diagnosis of second primary cancer were also calculated. Results: Between 1992 - 2017, 227,313 US women were diagnosed with an index gynecological cancer and 1,483,016 were diagnosed with an index non-gynecologic cancer. Among patients with index gynecologic cancer, 7.78% developed a non-gynecologic subsequent primary cancer. The risk of developing any non-gynecologic cancer following an index gynecologic cancer was higher than the risk in the general population (SIR 1.05, 95% CI 1.04 - 1.07). Organs especially at risk were Thyroid (SIR 1.45), Colon and Rectum (SIR 1.23), and Urinary System (SIR 1.33). Among women diagnosed with an index non-gynecologic cancer, 0.99% were diagnosed with a subsequent gynecologic cancer. The risk of developing a gynecologic cancer following a non-gynecologic cancer was also elevated compared to the average risk of the general population (SIR 1.05, 1.03 - 1.07), with uterine cancer having the highest SIR of 1.13. Conclusion: The risk of a developing a second primary cancer and the corresponding survival time is based on the order and site of the index and subsequent cancer. Surveillance guidelines should be examined further to optimize survivorship programs.

Disparities in adjuvant treatment of high-grade endometrial cancer in the Medicare population.

BACKGROUND: Black women experience worse survival effects with high-grade endometrial cancer. Differences in adjuvant treatment have been proposed to be major contributors to this disparity. However, little is known about the differences in type or timing of adjuvant treatment as it relates to race and ethnicity in the Medicare population. OBJECTIVE: This study aimed to examine patterns of adjuvant therapy and survival for non-Hispanic Black women vs non-Hispanic White women and Hispanic women who have undergone surgery for high-grade endometrial cancer in the Medicare population. STUDY DESIGN: We used the Medicare-linked Surveillance, Epidemiology, and End Results database to identify women who underwent surgery as a primary treatment for uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear-cell carcinoma, or serous carcinoma between the years 2000 and 2015. Women who did not identify as White or Black race or Hispanic ethnicity were excluded. Multinomial logistic regression was used to estimate odds ratios and 95% confidence intervals for receiving a treatment delay or not receiving adjuvant treatment (compared with those who received adjuvant treatment within 12 weeks) adjusted for clinical and demographic characteristics. Overall survival was stratified by race and ethnicity, route of surgery, operative complications, and type and timing of adjuvant therapy, which were analyzed using the Kaplan-Meier method. Cox proportional-hazards regression was used to estimate the hazard ratio of death by race and ethnicity adjusted for known predictors and surgical outcomes and adjuvant therapy patterns. RESULTS: A total of 12,201 women met the study inclusion criteria. Non-Hispanic Black patients had a significantly worse 5-year overall survival than Hispanic and non-Hispanic White patients (30.9 months vs 51.0 months vs 53.6 months, respectively). Approximately 632 of 7282 patients (8.6%) who received adjuvant treatment experienced a treatment delay. Delay in treatment of ≥12 weeks was significantly different by race and ethnicity (P=.034), with 12% of Hispanic, 9% of non-Hispanic Black, and 8% of non-Hispanic White women experiencing a delay. After adjustment for the number of complications, age, histology (endometrioid vs nonendometroid), International Federation of Gynecology and Obstetrics stage, marital status, comorbidity count, surgical approach, lymph node dissection, and urban-rural code, Hispanic women had a 71% increased risk of treatment delay (odds ratio, 1.71; 95% confidence interval, 1.23-2.38) for all stages of disease. In the same model, non-Hispanic Black race was independently predictive of decreased use of adjuvant treatment for the International Federation of Gynecology and Obstetrics stage II and higher (odds ratio, 1.32; 95% confidence interval, 1.04-1.68). Non-Hispanic Black race, number of perioperative complications, and nonendometrioid histology were predictive of worse survival in univariate models. Treatment delay was not independently predictive of worse 1- or 5-year survival at any stage. CONCLUSION: Non-Hispanic Black race was predictive of worse 5-year survival across all stages and was associated with omission of adjuvant treatment in International Federation of Gynecology and Obstetrics stage II or higher high-grade endometrial cancer. In unadjusted analyses, patients who experience treatment omission or delay experienced poorer overall survival, but these factors were not independently associated in multivariate analyses. This study suggests that race and ethnicity are independently associated with the type and timing of adjuvant treatment in patients with high-grade endometrial cancer. Further efforts to identify specific causes of barriers to care and timely treatment are imperative.

Using Technology to Improve Women's Health Care.

Background: Technology is being integrated into all aspects of health care. While many applications offer novel experiences, the evidence supporting translation to improved education or care is evolving. Methods: We review ways that technology is affecting a variety of fields pertinent to women's health, including patient communication, physician education, and health care performance. Results: In the Ochsner Health Department of Obstetrics and Gynecology, we have developed a platform known as Connected Maternity Online Monitoring-Connected MOM-to encourage remote monitoring during the prenatal course. We are also assessing improvements in quality and safety through a centralized fetal heart rate monitoring bunker known as TeleStork. Conclusion: Through systematic integration of technology into the delivery of women's health care at Ochsner, we hope to demonstrate sustainable improvements in physician skills, patient access, and quality and safety.