Military Medicine

Recommendation for Human Papillomavirus Vaccine after Abnormal Pap Smear in Unvaccinated Active Duty Women

Abstract Introduction Human Papillomavirus (HPV) is the most common sexually transmitted infection globally, with millions of new cases reported each year. Human Papillomavirus is associated with cervical, anal, vulva, penile, and esophageal cancer. Cervical cancer is a significant threat to women because of its insidious nature; thus, cervical cancer screening remains crucial for early detection and intervention. The most effective method to protect against HPV-related cancers is through vaccination with the HPV vaccine. The Human Papillomavirus vaccine targets the most common high-risk HPV strains. Vaccination is recommended for both males and females between the ages of 9-26. Vaccination reduces the risk of infection and contributes to the prevention of HPV-related cancers, representing a crucial public health initiative in battling HPV. The active duty military population has low HPV vaccination rates. A visit for a pap smear, the screening for cervical cancer, is an optimal time for providers to discuss the HPV vaccine. This research aims to understand the low HPV vaccination rate among active duty women and whether providers are maximizing opportunities to promote vaccination against HPV. Materials and Methods A retrospective medical chart review was performed at a single military treatment facility (MTF) of active duty women between the ages of 21-26, who had an abnormal pap smear, and no record of receiving the HPV vaccine. A chart review was conducted for the visit in which the pap smear was performed, as well as the follow-up visit/phone call to discuss the abnormal pap smear results. Results Seven hundred fifty-one charts were reviewed from 2005 to 2021 of unvaccinated active duty women with an abnormal pap smear. 46.3% of the abnormal pap smears were low-grade squamous intraepithelial cells (LGSIL), whereas 3.3% were high-grade squamous intraepithelial cells (HGSIL). Of the charts reviewed, 8.3% of the patients noted they had been vaccinated; 13.8% of the charts had documented recommendations for the HPV vaccination; and 77.9% had no documentation regarding the patient’s HPV status or recommendation for vaccination. Conclusion Although the HPV vaccine is effective in reducing the risk of HPV-related cancers, our results indicate the need for increased awareness and education practices amongst providers in promoting the HPV vaccine. A limitation of the study was that it was conducted at a single MTF. The study was not able to distinguish between provider types or clinic settings. Possible proposals for future studies include evaluating why the HPV vaccination rates amongst the active duty population are low. Pap smears are a prime opportunity for providers to engage in discussion of the importance of the HPV vaccine and encourage adherence.

Surgical Management of Endometrial Intraepithelial Neoplasia at Military Treatment Facilities: A Multicenter Retrospective Study

ABSTRACT Introduction Endometrial intraepithelial neoplasia (EIN), also known as atypical endometrial hyperplasia (AEH), is a precursor lesion of endometrial carcinoma (EC). In endometrial cancer patients, lymph node assessment with biopsy during hysterectomy is part of surgical staging. However, routine lymph node assessment for EIN is inconsistently utilized. This study aims to investigate the surgical management of EIN in the military to inform best-practice guidelines tailored for the Military Health System to avoid delays in care, manage cost, ensure military readiness and optimize clinical outcome. Materials and Methods We performed a retrospective chart review of patients with EIN treated at 2 military treatment facilities over a 10-year period between July 1, 2013 and July 1, 2023. Pathology reports were queried to identify patients with a preoperative diagnosis of EIN. Patients not surgically managed were excluded. Statistical analysis was performed using chi-squared test and Wilcoxon rank-sum test. Independent associations were investigated using logistic regression modeling. Results There were 95 evaluable patients with an EIN diagnosis, including 43 (45.3%) patients upstaged to EC based on final pathology (95% CI: 35.0-55.8). Older patients diagnosed with EIN ≥65 years old and those with endometrial thickness ≥15 mm exhibited the highest risk for upstaging EIN to an EC diagnosis. Of the 50 patients who underwent lymph node assessment, none had positive lymph nodes. Patients diagnosed with EIN via hysteroscopy vs. an endometrial biopsy had the lowest risk of being upstaged to EC. Conclusions Upstaging from EIN to EC occurred in 45.3% of the 95 patients emphasizing the value of performing surgicopathologic staging in this setting. In contrast, none of the 50 EIN patients who underwent lymph node resection had positive lymph nodes indicating morbidity risk with low likelihood of clinical benefit. We identified risk factors for upstaging to EC, including age ≥65 years and endometrial thickness ≥15 mm, and confirmed the diagnostic superiority of hysteroscopy. These findings have informed clinical practice guideline recommendations for the surgical management of EIN in the Military Health System.

The Mitigation of Racial Disparities in Cervical Cancer Screening Among U.S. Active Duty Service Women

ABSTRACT Introduction The U.S. Preventive Services Task Force recommends regular cervical cancer screening for women aged 21-65 years. Such screening is key to reducing mortality and morbidity. Despite improvement in the screening rate, cervical cancer still disproportionately affects women of minority groups because of access to quality health care. The Military Health System (MHS) mitigates this barrier through universal healthcare coverage for all active duty service members and their families. However, such racial/ethnic disparities, seen in civilian population, have not been studied in the MHS. Materials and Methods This is a retrospective cross-sectional study utilizing fiscal years 2011-2016 claims data obtained from the MHS Data Repository for 112,572 active duty service women aged 21-64 years. Study analyses included descriptive statistics on patient demographics, calculations of the proportion of patients who received cervical cancer screenings as well as the proportion of patients in compliance with USPSTF guidelines, and unadjusted odds ratios for the likelihood of compliance by race and military service. Results Of the study population, 50.0% of active duty women were screened for cervical cancer. When compared to White women, Black (1.05 OR, 1.03-1.08 CI), Native American/Alaskan Native (1.26 OR, 1.15-1.39 CI), and Other (1.12 OR, 1.06-1.18 CI) women were significantly more likely to receive cervical cancer screenings. The proportions of 3-year compliance were relatively equal within each race category (ranging from 43% to 45%), with no significant findings for the odds of compliance in any race when compared to White active duty women; however, proportions of 3-year compliance by service ranged from 11.7% in the Marines to 84.4% in the Navy, and active duty women in the Navy were six times more likely to be in compliance with guidelines than women in the Army. When looking at 5-year compliance in active duty women aged 30-64 years, women in the Navy were more likely than women in the Army to meet compliance guidelines (1.24 OR, 1.14-1.36 CI), while women in the Air Force were slightly less likely (0.90 OR, 0.82-0.98 CI). Conclusions The women in our population demonstrated similar or lower compliance than other studies conducted in the U.S. general population, and racial disparities for cervical cancer screening were partially mitigated in active duty service women. While our research demonstrates that universal insurance can help provide equal access and care, investigation into the factors that encourage greater usage among members of different military branches may help to understand and develop policies to improve health care systems.

Superior Survival Outcomes of Epithelial Ovarian Cancer Patients in the Universal Access Military Healthcare System Compared With the National Surveillance, Epidemiology, and End Results Program

Abstract Introduction To compare 5-year overall survival outcomes in patients diagnosed with epithelial ovarian carcinoma in the United States Department of Defense (DoD) cancer registry, who received universal healthcare, with the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, the U.S. general population. Materials and Methods Eligible patients were diagnosed with invasive stage I-IV epithelial ovarian carcinoma between 1987 and 2013. Each patient from the Automated Center Tumor Registry (ACTUR) for the DoD managed by the Joint Pathology Center was matched in a 1:4 ratio with stratification for age group, race, year of diagnosis, histology, and to patients in the 18-region SEER program. Five-year overall survival was evaluated using the Kaplan-Meier method and compared using log-rank test. Adjusted hazard ratio (AHR) and 95% CI for all-cause death in ACTUR compared with SEER were estimated from multivariable Cox proportional regression modeling controlling for age, race, year of diagnosis, region of diagnosis, stage, histology, and grade. Results There were 1,504 and 6,016 patients from ACTUR and SEER, respectively. Epithelial ovarian cancer patients in ACTUR had better 5-year overall survival than those in SEER (53.2% vs. 47.7%, log-rank P = .0010). The AHR (95% CI) was 0.83 (0.76-0.91, P < .0001) for ACTUR versus SEER patients after adjustment for age, race, year of diagnosis, region, histology, tumor stage, and grade. Subset analysis revealed that the reduced adjusted risk of death in ACTUR versus SEER patients with epithelial ovarian cancer remained significant in the subset diagnosed either at 35-49 years old (AHR = 0.66, 95% CI = 0.52-0.83; P = .0005) or 65+ years old (AHR = 0.82, 95% CI = 0.70-0.96; P = .016), or with stage III disease (AHR = 0.79, 95% CI = 0.69-0.91, P = .002), the clear cell carcinoma subtype (AHR = 0.63, 95% CI = 0.43-0.93; P = .02) or the adenocarcinoma subtype (AHR = 0.68, 95% CI = 0.56-0.81; P < .0001). There was also exploratory evidence for a trend for decreased adjusted risk of death in the subset of patients diagnosed between 50 and 64 years old (adjusted HR = 0.88, 95% CI = 0.77-1.01), with stage IV disease (adjusted HR = 0.87, 95% CI = 0.56-1.02), or with the serous adenocarcinoma subtype (adjusted HR = 0.92, 95% CI = 0.82-1.03). Adjusted risk of death was similar for ACTUR versus SEER patients diagnosed <35 years old (adjusted HR = 1.30, 95% CI = 0.68-2.47), with stage I disease (adjusted HR = 0.76, 95% CI = 0.51-1.14), with stage II disease (adjusted HR = 0.74, 95% CI = 0.47-1.16) or with the mucinous carcinoma subtype (adjusted HR = 0.93, 95% CI = 0.60-1.43). Conclusions Patients with epithelial ovarian carcinoma in the DoD Cancer Registry had better 5-year overall survival compared with a matched sample of patients from the national SEER program. The reduced lethality associated with epithelial ovarian cancer overall and in a range of subsets in the universal access to care Military Health System reinforces the value of maintaining readiness, medical skills, educational programs, and superior outcomes for gynecologic cancer care within the Defense Health Agency.

Cancer Previvors in an Active Duty Service Women Population: An Opportunity for Prevention and Increased Force Readiness

Abstract Background The majority of active duty service women (ADS) are young, have access to healthcare, and meet fitness standards set by the U.S. military, suggesting that ADS represent a healthy population at low risk of cancer. Breast cancer is, however, the most common cancer in ADS and may have a significant effect on troop readiness with lengthy absence during treatment and inability to return to duty after the treatment. The identification of unaffected ADS who carry germline mutations in cancer predisposition genes (“previvors”) would provide the opportunity to prevent or detect cancer at an early stage, thus minimizing effects on troop readiness. In this study, we determined (1) how many high-risk ADS without cancer pursued genetic testing, (2) how many previvors employed risk-reducing strategies, and (3) the number of undiagnosed previvors within an ADS population. Methods The Clinical Breast Care Project (protocol WRNMMC IRB #20704) database of the Murtha Cancer Center/Walter Reed National Military Medical Center was queried to identify all ADS with no current or previous history of cancer. Classification as high genetic risk was calculated using National Comprehensive Cancer Network 2019 guidelines for genetic testing for breast, ovary, colon, and gastric cancer. The history of clinical genetic testing and risk-reducing strategies was extracted from the database. Genomic DNA from ADS with blood specimens available for research purposes were subjected to next-generation sequencing technologies using a cancer predisposition gene panel. Results Of the 336 cancer-free ADS enrolled in the Clinical Breast Care Project, 77 had a family history that met National Comprehensive Cancer Network criteria for genetic testing for BRCA1/2 and 2 had a family history of colon cancer meeting the criteria for genetic testing for Lynch syndrome. Of the 28 (35%) high-risk women who underwent clinical genetic testing, 11 had pathogenic mutations in the breast cancer genes BRCA1 (n = 5), BRCA2 (n = 5), or CHEK2 (n = 1). Five of the six ADS who had a relative with a known pathogenic mutation were carriers of the tested mutation. All of the women who had pathogenic mutations detected through clinical genetic testing underwent prophylactic double mastectomy, and three also had risk-reducing salpingo-oophorectomy. Two (6%) of the 33 high-risk ADS tested only in the research setting had a family history of breast/ovarian cancer and carried pathogenic mutations: one carried a BRCA2 mutation, whereas the other carried a mutation in the colon cancer predisposition gene PMS2. No mutations were detected in the 177 low-risk women tested in the research setting. Discussion Within this unaffected cohort of ADS, 23% were classified as high risk. Although all of the previvors engaged in risk-reduction strategies, only one-third of the high-risk women sought genetic testing. These data suggest that detailed family histories of cancer should be collected in ADS and genetic testing should be encouraged in those at high risk. The identification of previvors and concomitant use of risk-reduction strategies may improve health in the ADS and optimize military readiness by decreasing cancer incidence.

HPV-Related Cancers: A Growing Threat to U.S. Military Health and Readiness

ABSTRACT The incidence of human papillomavirus (HPV) related cancers is growing in the United States. Active duty service members (ADSM) have higher rates of HPV infection than civilians and are therefore at greater risk of developing HPV-related cancers. The purpose of this commentary is to examine the burden of HPV-related cancers in ADSM. The current HPV vaccination and cervical cancer screening uptake rates of U.S. ADSM are presented, including a literature review of military-focused studies on HPV vaccination and cervical cancer screenings. We provide directions for future research, interventions, and policy recommendations to improve HPV-related cancer prevention among ADSM.

Editorial on “The Mitigation of Racial Disparities in Cervical Cancer Screening Among US Active Duty Service Women”

Management of Endometrial Cancer Precursors in the Military Health System: A Survey-Based Study

ABSTRACT Introduction Endometrial intraepithelial neoplasia (EIN) and atypical endometrial hyperplasia (AEH) are precancerous pathologies which carry a 40-50% concurrent cancer incidence. National guidelines recommend an individualized approach to gynecologic oncologist (GO) referral for a new EIN-AEH diagnosis. With the risk of underlying carcinoma, exactly who should manage EIN-AEH is controversial. In the military health system, gynecologic specialists (GS) may be remote with significant barriers to GO consultation, presenting a complex medical and social burden with potential impact to mission readiness. To our knowledge, no study has evaluated EIN-AEH practice patterns in the military health system. As practice patterns may vary, we surveyed EIN-AEH management by active duty GS and GO. Materials and Methods An observational, voluntary, tri-service, survey-based study was conducted (eIRB protocol #966986) using two web-based surveys designed by military GO: one completed by active duty GS, the other by active duty GO. Demographics examining influential factors were collected. Surveys examined attitudes and practice patterns regarding referral and management of EIN-AEH. Univariate analysis was performed. Results Of eligible physicians, 72 of 269 GS (26.8%) and 18 of 19 GO (94.7%) responded. More than 80% of GS/GO completed military medical training (81.9% vs. 88.9%), 72.2% vs. 61.1% were specialty-specific board-certified, 72.2% vs. 88.9% had a CONUS assignment, and 52.8% vs. 100% were part of large gynecologic surgery and obstetrics (GS&O) departments, respectively. Most GS (61.1%) had access to a GO at their facility or within 60 miles and 56.9% had no formal EIN-AEH policy. Half of GS (50%) were willing to manage EIN-AEH in an appropriately counseled and biopsied patient; however, less than a quarter (23.6%) felt comfortable with fertility-sparing management. Most GS (68%) were willing to perform EIN-AEH surgical management if GO back-up was available and 83.5% of GOs indicated willingness to provide virtual consultation. When offered co-management with GO virtual consultation, GS expressed a 3-fold increased comfort with hysterectomy surgical management, including those stationed overseas (OR = 3.10; 95% CI = 1.55-6.21, P < .0014; overseas P = NS), and an 8-fold increased comfort with fertility-sparing management (OR = 7.86; 95% CI = 3.73-16.4, P < .0001). Conclusions Management and referral of EIN-AEH by military GS varies widely with no policy at most facilities. A solution is needed, particularly in remote and overseas locations, to reduce medical, health system and social burden, and to conserve the fighting strength.

Best Practice Recommendations for Endometrial Intraepithelial Neoplasia/Atypical Endometrial Hyperplasia in the Military Health System

ABSTRACT Endometrial cancer is the most prevalent gynecologic cancer in the United States and has rising incidence and mortality. Endometrial intraepithelial neoplasia or atypical endometrial hyperplasia (EIN-AEH), a precancerous neoplasm, is surgically managed with hysterectomy in patients who have completed childbearing because of risk of progression to cancer. Concurrent endometrial carcinoma (EC) is also present on hysterectomy specimens in up to 50% of cases. Conservative medical management with progestins and close surveillance can be employed for certain populations after evaluating for concurrent EC. Currently, national professional guidelines recommend an individualized approach based on community access to care and patient factors. There is, however, no US civilian consensus on who should primarily manage EIN-AEH: Physician gynecologic specialists (GSs) and/or gynecologic oncologist (GO) subspecialists. Military health care presents an additional challenge with beneficiaries stationed at remote or overseas locations. While patients may not have local access to a GO subspecialist, many locations are staffed with GSs. Travel for care with a GO incurs additional cost for the patient and the military health care system, removes patients from local support systems, and can impact mission readiness. To provide the best care, optimize clinical outcomes, and avoid over- or under-treatment, military-specific guidelines for EIN-AEH management are needed. We propose a clinical decision tree incorporating both GS and GO subspecialists in the care of military beneficiaries with EIN-AEH. The subject matter expert panel recommends referral of EIN-AEH to a military (preferrable) or civilian GO for management if local access is available within 100 miles[Q1] . If travel of >100 miles is required, the patient should be offered the choice of a military GO referral if available within 250 miles (preferred) versus management by a GS. If travel is >100 miles from a GO or the patient declines a GO referral, the panel recommends that the GS should attempt to exclude concurrent EC by performing a hysteroscopic assessment of the endometrium with a directed biopsy, if not already done. A pelvic ultrasound should be obtained to evaluate the endometrial thickness (>2 cm more likely to harbor EC) along with a secondary gynecologic pathology review with immunohistochemical testing for Lynch syndrome (MLH1, MSH2, MSH6, and PMS2) and p53 expression. If any major additional risk factors are uncovered, the patient should be referred to a GO subspecialist for further management. If no additional major risk factors for concurrent EC are identified and hysteroscopy with expert gynecologic pathology review confirms no presence of EC in the pathology specimen, a virtual consultation and counseling with a military GO can be offered, with local surgical and/or medical management provided by a GS. If on subsequent pathology, EC is identified, the patient should be referred to a GO for further treatment considerations and counseling. Determining the optimal treatment for patients with EIN-AEH is nuanced and, within the military health care system, is complicated by varied access to expert management by a GO subspecialist. Military beneficiaries with this diagnosis present a unique challenge and warrant a standardized approach to maximize clinical outcomes.

Mandatory HPV Vaccination; Opportunity to Save Lives, Improve Readiness and Cut Costs

ABSTRACT Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the U.S. military and accounts for more healthcare visits than the next two most common STIs combined. Human papillomavirus is preventable with a safe, effective, prophylactic vaccine that has been available since 2006, yet vaccination rates remain low. The vaccine is approved for females and males aged 9-45 years for prevention of HPV-related dysplasia and cancers. Although it is recommended by the Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP), it is not part of the U.S. military’s mandatory vaccine list. Human papillomavirus does not just affect female service members—male service members have a higher reported seropositive rate than their civilian counterparts and can develop oropharyngeal, anal, or penile cancers as sequelae of HPV. Oropharyngeal cancer, more common in males, is the fastest growing and most prevalent HPV-related cancer in the USA. Several countries, such as Australia and Sweden, have successfully implemented mandatory vaccine programs and have seen rates of HPV-related diseases, including cancer, decline significantly. Some models project that cervical cancer, which is the fifth-most common cancer in active duty women, will be eliminated in the next 20 years as a result of mandatory vaccination programs. Between higher seropositive rates and lack of widespread vaccination, HPV dysplasia and cancer result in lost work time, decreased force readiness, negative monetary implications, and even separation from service. With more than half of the 1.3 million service members in the catch-up vaccination age range of less than 26 years of age, we are poised to have a profound impact through mandatory active duty service member vaccination. Although multiple strategies for improving vaccination rates have been proposed, mandatory vaccination would be in line with current joint service policy that requires all ACIP-recommended vaccines. It is time to update the joint service guidelines and add HPV vaccine to the list of mandatory vaccines.

Improving Breast and Cervical Cancer Screening Compliance Through Direct Physician Contact in a Military Treatment Facility: A Non-randomized Pilot Study

ABSTRACTIntroductionScreening for breast cancer (BC) and cervical cancer (CC) decreases morbidity and mortality. Most interventions to improve screening rely on automated modalities or nonphysician patient contact. There is limited data on direct patient contact by a physician to encourage BC and CC screening. This non-randomized pilot study sought to evaluate the potential of direct physician contact to improve BC and CC screening rates.Materials and MethodsA Family Medicine physician telephoned patients on his panel who were due or overdue for BC and CC screening. If the patient did not answer her phone, a voicemail was left; if unable to leave a voicemail, a letter was mailed. The completion rate of recommended screening tests was measured 3 months after contact and compared to a retrospectively identified control population. The change in compliance of the patient panel over 3 months was also calculated.ResultsDirect physician conversation by telephone yielded higher completion rates for BC and CC screening versus control patients, but only the CC completion rate increase was statistically significant. Direct conversation BC screening completion rate: 41.2% versus 22.7% (P = .22, n = 48). Direct conversation CC screening completion rate: 45% versus 13.9% (P = .01, n = 44). The intervention patient panel compliance with screening recommendations increased 20.5% for BC and 10.5% for CC.ConclusionDirect physician contact may be beneficial to increase compliance for more invasive screening tests.