Consuming Patients' Days: Time Spent on Ambulatory Appointments by People With Cancer.

BACKGROUND: In qualitative work, patients report that seemingly short trips to clinic (eg, a supposed 10-minute blood draw) often turn into "all-day affairs." We sought to quantify the time patients with cancer spend attending ambulatory appointments. METHODS: We conducted a retrospective study of patients scheduled for oncology-related ambulatory care (eg, labs, imaging, procedures, infusions, and clinician visits) at an academic cancer center over 1 week. The primary exposure was the ambulatory service type(s) (eg, clinician visit only, labs and infusion, etc.). We used Real-Time Location System badge data to calculate clinic times and estimated round-trip travel times and parking times. We calculated and summarized clinic and total (clinic + travel + parking) times for ambulatory service types. RESULTS: We included 435 patients. Across all service day type(s), the median (IQR) clinic time was 119 (78-202) minutes. The estimated median (IQR) round-trip driving distance and travel time was 34 (17-49) miles and 50 (36-68) minutes. The median (IQR) parking time was 14 (12-15) minutes. Overall, the median (IQR) total time was 197 (143-287) minutes. The median total times for specific service type(s) included: 99 minutes for lab-only, 144 minutes for clinician visit only, and 278 minutes for labs, clinician visit, and infusion. CONCLUSION: Patients often spent several hours pursuing ambulatory cancer care on a given day. Accounting for opportunity time costs and the coordination of activities around ambulatory care, these results highlight the substantial time burdens of cancer care, and support the notion that many days with ambulatory health care contact may represent "lost days."

Rural-urban differences in meeting of physical activity recommendations by sun exposure and protection behaviors in the United States.

OBJECTIVE: To examine associations between sun protection behaviors and physical activity (PA) by rural and urban residence in the United States. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (2013-2018), restricting to participants ages 20-59 with sun behavior data. Sunburns, sun exposure, and sun protection measures were dichotomized (yes/no): ≥1 sunburn in the past year, 2+ hour outside during workdays or non-workdays, and never/rarely/sometimes using sunscreen, wearing long sleeves, and staying in the shade. Meeting PA recommendations (yes/no) was defined as ≥150 min of vigorous/moderate or ≥ 75 min vigorous PA per week. Associations between sun behaviors and PA were analyzed using logistic regression models, which accounted for survey-weights and potential confounders, and stratified by rural-urban status. RESULTS: Rural and urban individuals meeting PA recommendations had greater odds of spending 2+ hour outside during workdays (OR: 2.26 [1.88, 2.74] and 3.95 [2.72, 5.73]) and non-workdays (OR: 2.06 [1.78, 2.38] and 3.33 [2.47, 4.46]). Among urban residents, odds of staying in the shade were lower among those who met PA recommendations (OR: 0.78 [0.66, 0.92]). We did not observe differences in sunburns or other sun behaviors by PA status, regardless of rurality. CONCLUSIONS: Meeting PA recommendations was associated with greater sun exposure in both rural and urban populations. Additional exercise location (indoors/outside) data is needed to inform PA and skin cancer prevention interventions to reduce unintended increases in sun exposure and reductions in PA, respectively, especially among rural populations.

Effects of Exposure to Conflicting Health Information on Topic-Specific Information Sharing and Seeking Intentions.

Despite considerable evidence that exposure to conflicting health information can have undesirable effects on outcomes including public understanding about and trust in health recommendations, comparatively little is known about whether such exposure influences intentions to engage in two communication behaviors central to public health promotion: information sharing and information seeking. The purpose of the current study is to test whether exposure to conflicting information influences intentions to share and seek information about six health topics. We analyzed data from two waves of a longitudinal survey experiment with a nationally representative sample of U.S. adults (N = 3,920). Participants were randomly assigned to either a conflict or no-conflict message condition, in which they read news stories and social media posts about three (of six) randomly selected health topics at Time 1 and the remaining three at Time 2. The dependent variables, which were measured at Time 2, asked participants whether they intended to share or seek information about the three topics they had just viewed. Linear mixed effects models showed that exposure to conflict reduced intentions to share and seek information, regardless of health topic. These findings suggest that exposure to conflicting health information discourages two important types of health information engagement, thus adding to the growing evidence base documenting the adverse consequences of conflicting information for public health.

Prevalence of active cytomegalovirus infection at diagnosis of ovarian cancer and during chemotherapy and subsequent changes in cognitive functioning.

PURPOSE: One of the most frequently reported effects of cancer and its treatments is cancer-related cognitive impairment (CRCI). Viral infections may affect inflammation and immune function and therefore may influence patient symptoms, including CRCI. The goal of this study was to describe the prevalence of cytomegalovirus (CMV) infections at diagnosis, during, and after chemotherapy in individuals with ovarian cancer and explore CMV infection at diagnosis with cancer-related cognitive impairment (CRCI) following chemotherapy. METHODS: We recruited adults newly diagnosed with ovarian, primary peritoneal or fallopian tube cancer at a single academic cancer center into two prospective studies. In Study 1 (N = 71), participants provided blood samples at diagnosis. In Study 2 (N = 18), participants provided blood samples and completed symptom surveys before, during and after front-line adjuvant chemotherapy. Serum CMV DNA levels were assessed using digital PCR; >100 copies/mL of serum was considered positive for active CMV infection (CMV+). CRCI was measured using the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) questionnaire. Changes in FACT-Cog scores were compared by CMV status at diagnosis using t-tests at each time point. RESULTS: At diagnosis, 29.2% were CMV+ (28.2% in Study 1, 33.3% in Study 2). Following three cycles of chemotherapy (Study 2), CMV positivity rose to 60.0% and then back down to 31.3% after chemotherapy. We observed significant differences in CRCI following chemotherapy by CMV status at diagnosis. CONCLUSION: Our data suggest that active CMV infection is common among patients undergoing treatment for ovarian cancer and may contribute to symptoms of CRCI.

Genetic variants associated with post-traumatic stress symptoms in patients with gynecologic cancer.

OBJECTIVE: Patients with cancer experience symptoms of post-traumatic stress disorder (PTSD) more commonly than the general population. The objective of this study was to identify single nucleotide polymorphisms (SNPs) associated with increased risk of post-traumatic stress disorder (PTSD) in patients with gynecologic cancer. METHODS: A prospective cohort study recruited 181 gynecologic cancer survivors receiving care at the University of Minnesota between 2017 and 2020 who completed PTSD DSM-V surveys to self-report their symptoms of PTSD and provided saliva samples. DNA samples were genotyped for 11 SNPs in 9 genes involved in dopaminergic, serotonergic, and opioidergic systems previously associated with risk of PTSD in populations without cancer. RESULTS: Most participants had either ovarian (42.5%) or endometrial (46.4%) cancer; fewer had cervical (7.7%) or vaginal/vulvar (3.3%) cancer. Two SNPS were identified as statistically significantly associated with higher PTSD scores: rs622337 in HTR2A and rs510769 in OPRM1. CONCLUSIONS: Genetic variation likely plays a role in development of PTSD. HTR2A is involved in the serotonin pathway, and OPRM1 is involved in the opioid receptor pathway. This information can be used by oncologic providers to identify patients at greater risk of developing PTSD and may facilitate referral to appropriate consultants and resources early in their treatment.

DNA Deamination Is Required for Human APOBEC3A-Driven Hepatocellular Carcinoma In Vivo.

Although the APOBEC3 family of single-stranded DNA cytosine deaminases is well-known for its antiviral factors, these enzymes are rapidly gaining attention as prominent sources of mutation in cancer. APOBEC3's signature single-base substitutions, C-to-T and C-to-G in TCA and TCT motifs, are evident in over 70% of human malignancies and dominate the mutational landscape of numerous individual tumors. Recent murine studies have established cause-and-effect relationships, with both human APOBEC3A and APOBEC3B proving capable of promoting tumor formation in vivo. Here, we investigate the molecular mechanism of APOBEC3A-driven tumor development using the murine Fah liver complementation and regeneration system. First, we show that APOBEC3A alone is capable of driving tumor development (without Tp53 knockdown as utilized in prior studies). Second, we show that the catalytic glutamic acid residue of APOBEC3A (E72) is required for tumor formation. Third, we show that an APOBEC3A separation-of-function mutant with compromised DNA deamination activity and wildtype RNA-editing activity is defective in promoting tumor formation. Collectively, these results demonstrate that APOBEC3A is a "master driver" that fuels tumor formation through a DNA deamination-dependent mechanism.

The intersection of sexual orientation with race and ethnicity in cervical cancer screening.

BACKGROUND: Cervical cancer screening is recommended for those with a cervix who are 21 to 65 years old, with specific timelines being dependent on individual risk. This study compared rates of ever undergoing Papanicolaou (Pap) testing at the intersection of self-reported sexual minority (SM) status and race/ethnicity. METHODS: Data from the National Health Interview Survey (2015 and 2018) were used to examine cervical cancer screening disparities. Natal females without a history of hysterectomy who were 21 to 65 years old and had reported their sexual orientation and Pap testing history were included. Demographic and health characteristics were summarized with descriptive statistics. To adjust for differences in confounding variables between groups, propensity score-based inverse probability of treatment weighting (IPTW) was performed. IPTW-adjusted multivariable logistic regression models estimated odds of ever undergoing a Pap test by sexual orientation alone and with race/ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic). RESULTS: SM persons (n = 877) had significantly reduced odds of ever undergoing Pap testing (odds ratio, 0.54; 95% confidence interval, 0.42-0.70) in comparison with heterosexual persons (n = 17,760). When the intersection of sexual orientation and race/ethnicity was considered, non-Hispanic White SM participants and Hispanic SM participants had reduced odds of ever undergoing Pap testing in comparison with non-Hispanic White heterosexual participants. No significant differences were observed between non-Hispanic White heterosexual participants and participants of non-Hispanic Black SM or Hispanic heterosexual identities. CONCLUSIONS: SM participants were significantly less likely to have ever undergone a Pap test in comparison with heterosexual participants, with Hispanic SM participants having the lowest uptake. Future studies should further examine the roles of systemic discrimination and other key drivers of these disparities.

Perception of Telehealth During the COVID-19 Pandemic Among Survivors of Gynecologic Cancer.

Our objective was to assess gynecologic cancer survivor preferences for telehealth cancer care. Gynecologic cancer survivors participating in a prospective cohort study were invited to complete a cross-sectional survey regarding their experience with and preferences for telehealth. Of 188 participants, 48.9% had undergone a telehealth visit since March 2020, and 53.7% reported a preference for exclusively in-person visits for their cancer care and surveillance. Furthermore, 80.5% of participants were satisfied with the telehealth care they received and 54.8% would recommend telehealth services to patients with similar conditions. Most participants thought a physical examination was critical to detecting recurrence, and concern that their provider may miss something during telehealth visits was greater among those who preferred in-person visits. With many gynecologic cancer survivors preferring in-person care, building a future care model that includes telehealth elements will require adaptations, careful evaluation of patient concerns, as well as patient education on telehealth.

Robot-assisted versus laparoscopic minimally invasive surgery for the treatment of stage I endometrial cancer.

OBJECTIVE: Recent reports in both cervical and endometrial cancer suggest that minimally invasive surgery (MIS) had an unanticipated negative impact on long-term clinical outcomes, including recurrence and death. Given increasing use of robotic surgery since the LAP2 trial, we sought to compare the intermediate and long-term outcomes between those who underwent robotic surgery or laparoscopy for Stage I endometrial cancer. METHODS: We performed a retrospective review of patients from a single, large, academic, urban practice who underwent either laparoscopic or robot-assisted MIS (RA-MIS) for the treatment of endometrial carcinoma between 2006 and 2016, ensuring at least 5 years of potential follow-up. To adjust for differences in confounding variables between groups, propensity score-based inverse probability of treatment weighting (IPTW) was performed. Overall and recurrence-free survival were compared using Cox proportional hazards regression models adjusting for confounding weights. RESULTS: 1027 patients were included; 461 received laparoscopy and 566 received RA-MIS. RA-MIS use increased steadily during the study window, which resulted in longer mean surveillance in laparoscopy group (median 8.7 years versus 6.3 years, p < 0.001). RA-MIS was associated poorer recurrence-free (HR: 1.41, 95% CI: 1.12, 1.77) and overall survival (HR: 1.39, 95% CI: 1.06, 1.83). Disease-specific survival was also poorer in the RA-MIS group (HR: 3.51, 95% CI: 2.19, 5.63). Among those who recurred, median time to first recurrence was shorter in the RA-MIS group than the laparoscopy group (16.3 vs. 28.7 months, p = 0.07). CONCLUSION: RA-MIS was associated with poorer long-term patient outcomes. Our data in this lower-risk population indicate relevant clinical endpoints may be occurring during intermediate and long-term follow-up windows. These findings support a prospective evaluation of the long-term outcomes of RA-MIS.

Interactions between physical activity and type of cancer treatment received on associations with psychosocial outcomes among gynecologic cancer survivors.

OBJECTIVE: Physical activity is associated with improved cancer outcomes; however, it is unclear which patients may benefit most from increased physical activity. We evaluated whether associations between meeting the American Cancer Society (ACS) physical activity recommendations and psychosocial outcomes in gynecologic cancer survivors varied by type of treatments received. METHODS: We recruited English-speaking adult gynecologic cancer patients from an academic gynecologic oncology practice to participate in a prospective cohort study. Participants completed a survey at study entry regarding their psychosocial health-including distress, depression, anxiety, post-traumatic stress disorder, and quality of life (QoL)-and physical activity. Multivariate linear regression models for each psychosocial outcome tested for interactions between physical activity and each effect modifier (receipt of chemotherapy, radiation therapy, and/or minimally invasive surgery), adjusted for age, pain, body mass index, primary cancer diagnosis, cancer stage, time since diagnosis, and annual household income. RESULTS: Among a total of 362 participants, 213 (59%) met ACS physical activity recommendations. We found evidence of interactions between physical activity and receipt of chemotherapy for depression, anxiety, and QoL scores; those who had received chemotherapy had a stronger association between physical activity and these psychosocial outcomes, compared to those who had not. We found no evidence of interactions between physical activity and receipt of radiation therapy or minimally invasive surgery for any of the outcomes. CONCLUSIONS: Gynecologic cancer survivors who received chemotherapy had significant associations between psychosocial health and physical activity, suggesting they may derive greatest benefit from prescribed exercise.

Psychosocial predictors of fear of cancer recurrence in a cohort of gynecologic cancer survivors.

OBJECTIVE: To describe fear of cancer recurrence in a cohort of women with gynecologic cancers and to identify psychosocial predictors of elevated fear of recurrence. METHODS: Survey data from an ongoing cohort study of gynecologic cancer survivors were used (n = 154). Relationships between fear of cancer recurrence measured by the 6-item Cancer Worry Scale in the most recent survey and psychosocial factors (cancer-related distress, depression, anxiety, hopelessness, and posttraumatic growth) assessed 6-18 months prior were examined using univariate and multivariate linear regression models, adjusting for age, cancer stage, cancer type, and time since diagnosis. RESULTS: Most participants were ≥60 years old, diagnosed with early-stage cancer, and 2-5 years post-diagnosis. The mean score on the Cancer Worry Scale was 10.31 (SD = 3.01), and 46 individuals (30.0%) scored ≥12, indicating high fear of recurrence. In univariate analyses, greater distress (p = 0.007), anxiety (p = 0.006), hopelessness (p = 0.007), and posttraumatic growth (p = 0.0006) were significantly associated with higher scores on the Cancer Worry Scale. The associations of hopelessness and posttraumatic growth with higher Cancer Worry Scale scores remained significant after adjustment for covariates. CONCLUSIONS: Fear of recurrence is frequent among gynecologic cancer survivors. Women who reported more distress, hopelessness, anxiety and, surprisingly, more post-traumatic growth reported more fear. These results contribute to our understanding of which cancer survivors are most at risk of elevated fear of recurrence and highlight the importance of continued focus on psychosocial well-being among cancer survivors.

Effects of Prior Exposure to Conflicting Health Information on Responses to Subsequent Unrelated Health Messages: Results from a Population-Based Longitudinal Experiment.

BACKGROUND: Accumulating evidence suggests that exposure to conflicting health information can adversely affect public understanding of and trust in health recommendations. What is not known is whether prior exposure to such information renders people less receptive to subsequent unrelated health messages about behaviors for which the evidence is clear and consistent. PURPOSE: This study tests this "carryover" effects hypothesis, positing that prior exposure to conflict will reduce receptivity to subsequent unrelated health messages, and examines potential affective and cognitive pathways through which such effects might occur. METHODS: A three-wave, online, population-based survey experiment (N = 2,716) assessed whether participants who were randomly assigned to view a series of health news stories and social media posts featuring conflict at Times 1 and 2 were ultimately less receptive at Time 3 to ads from existing health campaigns about behaviors for which there is scientific consensus, compared to those who saw the same series of stories and posts that did not feature conflict. RESULTS: Structural equation modeling revealed evidence of carryover effects of exposure to conflict on two dimensions of message receptivity: greater resistance to the unrelated ads and lower perceptions of the health behaviors featured in the ads. Modeling indicated that carryover effects were a function of generalized backlash toward health recommendations and research elicited by prior exposure to conflicting information. CONCLUSIONS: Findings suggest that the broader public information environment, which is increasingly characterized by messages of conflict and controversy, could undermine the success of large-scale public health messaging strategies.

Americans' perceptions of health disparities over the first year of the COVID-19 pandemic: Results from three nationally-representative surveys.

COVID-19 has illuminated health inequity in the United States. The burdens of disease are much higher among Black and Indigenous people and other people of color. Disparities by income are also profound, as lower-wage workers were less able to adopt mitigating behaviors compared to higher-income counterparts. These disparities became part of public health discourse in 2020, with commentators frequently highlighting the connection between racism, socioeconomic position, and COVID-19. But what proportion of the public-and among key subgroups-recognized these social group disparities, relative to disparities associated with age and chronic illness, and did public recognition change over the first year of the pandemic? To address these questions, we analyzed data from three nationally-representative cross-sectional public opinion surveys, collected using the NORC AmeriSpeak panel in April 2020 (N = 1007), August 2020 (N = 2716), and April 2021 (N = 1020). The key outcomes were respondents' agreement with statements about disparities in COVID-19 mortality by age, chronic illness, income, and race. We found little change from 2020 to 2021 in Americans' recognition of disparities. At all three time points, most respondents acknowledged age and chronic illness disparities, while no more than half at any time point recognized income- and race-based disparities. Political party affiliation was not statistically associated with agreement with age or illness-related disparities, but was strongly associated with views about income- and race-based disparities. Efforts to promote recognition of racial and socioeconomic health disparities in the United States need to be mindful of the ways in which public understanding of health inequities is linked to partisanship.

Associations between a sense of connection and existential and psychosocial outcomes in gynecologic and breast cancer survivors.

BACKGROUND: A cancer diagnosis may lead to existential despair but potentially also to perceived inner growth. This growth may be fostered through meaningful connections with others. We sought to describe existential and related psychosocial outcomes and their association with a sense of connection with others in individuals with gynecological and breast cancers. METHODS: We used cross-sectional data from two ongoing cohort studies of gynecologic (N = 236) and breast (N = 62) cancer survivors at the University of Minnesota. We summarized self-reported post-traumatic growth (PTG), sense of meaning, peace, spirituality, hopelessness, loneliness, and three exploratory measures of sense of connections with others, and used multivariate linear regression models to describe the associations between them. RESULTS: Hope, sense of meaning, peace, and spirituality were generally high among participants, but PTG and loneliness scores varied more. Sense of connection with others was consistently associated with greater PTG and decreased loneliness with medium effect sizes: for example having positive interactions with most/all versus nobody on one's medical team, PTG (coefficient 10.49, 95% CI: 4.10, 16.87, Cohen's D 0.44); loneliness (coefficient - 0.85, 95% CI: - 1.36, - 0.34, Cohen's D 0.43). Those who knew someone in a similar life situation felt a strong sense of connection with such a person; however, 28% of participants had not met anyone in a similar situation. CONCLUSIONS: There may be untapped opportunities to nurture beneficial existential outcomes in cancer survivors. Potential interventions include connecting survivors with one another and creating opportunities for more authentic patient-provider relationships, for example, within palliative care.

The least costly pharmacy for cancer supportive care medications over time: the logistic toxicity of playing catch up.

PURPOSE: No single pharmacy in an urban zip code is consistently the least expensive across medications. If medication prices change differently across pharmacies, patients and clinicians will face challenges accessing affordable medications when refilling medications. This is especially pertinent to people with cancer with multiple fills of supportive care medications over time. We evaluated if the lowest-priced pharmacy for a formulation remains the lowest-priced over time. METHODS: We compiled generic medications used to manage nausea/vomiting (14 formulations) and anorexia/cachexia (12 formulations). We extracted discounted prices in October 2021 and again in March 2022 for a typical fill at 8 pharmacies in Minneapolis, Minnesota, USA (zip code 55,414) using GoodRx.com. We examined how prices changed across formulations and pharmacies over time. RESULTS: Data were available for all 208 possible pharmacy-formulation combinations (8 pharmacies × 26 formulations). For 172 (83%) of the 208 pharmacy-formulation combinations, the March 2022 price was within 20% of the October 2021 price. Across pharmacy-formulation combinations, the price change over time ranged from - 76 to + 292%. For 12 (46%) of the 26 formulations, at least one pharmacy with the lowest price in October 2021 no longer was the least costly in March 2022. For one formulation (dronabinol tablets), the least expensive pharmacy became the most expensive, with an absolute and relative price increase of a fill of $22 and 85%. CONCLUSION: For almost half of formulations studied, at least one pharmacy with the lowest price was no longer the least costly a few months later. The lowest price for a formulation (across pharmacies) could also change considerably. Thus, even if a patient accesses the least expensive pharmacy for a medication, they may need to re-check prices across all pharmacies with each subsequent fill to access the lowest prices. In addition to safety concerns, directing medications to and accessing medications at multiple pharmacies can add time and logistic toxicity to patients with cancer, their care partners, prescribers, and pharmacy teams.

JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors.

Tumor-associated macrophages contribute to tumor progression and therapeutic resistance in breast cancer. Within the tumor microenvironment, tumor-derived factors activate pathways that modulate macrophage function. Using in vitro and in vivo models, we find that tumor-derived factors induce activation of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway in macrophages. We also demonstrate that loss of STAT3 in myeloid cells leads to enhanced mammary tumorigenesis. Further studies show that macrophages contribute to resistance of mammary tumors to the JAK/STAT inhibitor ruxolitinib in vivo and that ruxolitinib-treated macrophages produce soluble factors that promote resistance of tumor cells to JAK inhibition in vitro. Finally, we demonstrate that STAT3 deletion and JAK/STAT inhibition in macrophages increases expression of the protumorigenic factor cyclooxygenase-2 (COX-2), and that COX-2 inhibition enhances responsiveness of tumors to ruxolitinib. These findings define a mechanism through which macrophages promote therapeutic resistance and highlight the importance of understanding the impact of targeted therapies on the tumor microenvironment.

Endogenous APOBEC3B overexpression characterizes HPV-positive and HPV-negative oral epithelial dysplasias and head and neck cancers.

The DNA cytosine deaminase APOBEC3B (A3B) is a newly recognized endogenous source of mutations in a range of human tumors, including head/neck cancer. A3B inflicts C-to-T and C-to-G base substitutions in 5'-TCA/T trinucleotide motifs, contributes to accelerated rates of tumor development, and affects clinical outcomes in a variety of cancer types. High-risk human papillomavirus (HPV) infection causes A3B overexpression, and HPV-positive cervical and head/neck cancers are among tumor types with the highest degree of APOBEC signature mutations. A3B overexpression in HPV-positive tumor types is caused by the viral E6/E7 oncoproteins and may be an early off-to-on switch in tumorigenesis. In comparison, less is known about the molecular mechanisms responsible for A3B overexpression in HPV-negative head/neck cancers. Here, we utilize an immunohistochemical approach to determine whether A3B is turned from off-to-on or if it undergoes a more gradual transition to overexpression in HPV-negative head/neck cancers. As positive controls, almost all HPV-positive oral epithelial dysplasias and oropharyngeal cancers showed high levels of nuclear A3B staining regardless of diagnosis. As negative controls, A3B levels were low in phenotypically normal epithelium adjacent to cancer and oral epithelial hyperplasias. Interestingly, HPV-negative and low-grade oral epithelial dysplasias showed intermediate A3B levels, while high-grade oral dysplasias showed high A3B levels similar to oral squamous cell carcinomas. A3B levels were highest in grade 2 and grade 3 oral squamous cell carcinomas. In addition, a strong positive association was found between nuclear A3B and Ki67 scores suggesting a linkage to the cell cycle. Overall, these results support a model in which gradual activation of A3B expression occurs during HPV-negative tumor development and suggest that A3B overexpression may provide a marker for advanced grade oral dysplasia and cancer.

Comparisons of emotional health by diagnosis among women with early stage gynecological cancers.

OBJECTIVE: To assess self-reported emotional health in a cohort of women with early stage gynecologic cancers and to explore differences based on primary cancer type. METHODS: We analyzed survey data from a cohort study of gynecological cancer patients treated at an academic cancer center. Measures of emotional health included cancer-related quality of life, distress, depression, anxiety, posttraumatic stress disorder (PTSD), and posttraumatic growth. Univariate and multivariate linear regression models examined differences in emotional health measures by primary cancer site. Potential confounders considered for inclusion in the final models were age, stage, education, income, partner status, treatment status, and race. RESULTS: 242 patients with early stage disease completed the survey. Patients with cervical and vaginal/vulvar cancers reported greater cancer-related distress, anxiety and PTSD symptoms. Patients with endometrial cancer reported the lowest posttraumatic growth scores, which remained statistically significant after adjustment for demographic and clinical differences. No significant differences in cancer-related quality of life were observed among individuals with different primary cancer sites CONCLUSIONS: These data suggest patients with early-stage gynecologic cancer face different psychosocial sequelae based on primary cancer site, though underlying clinical and sociodemographic factors may play a significant role in this observed relationship. Further research is needed to assess poorer emotional health among individuals with vaginal/vulvar cancers and the lower posttraumatic growth among patients with endometrial cancer as posttraumatic growth is considered a potentially beneficial psychosocial outcome of cancer.

Genetic variants predictive of chemotherapy-induced peripheral neuropathy symptoms in gynecologic cancer survivors.

OBJECTIVE: To identify genetic variants associated with chemotherapy-induced peripheral neuropathy (CIPN) symptoms among gynecologic cancer survivors and determine the variants' predictive power in addition to age and clinical factors at time of diagnosis. METHODS: Participants of a prospective cohort study on gynecologic cancers provided a DNA saliva sample and reported CIPN symptoms (FACT/GOG-Ntx). Genotyping of 23 single nucleotide polymorphisms (SNPs) previously identified as related to platinum- or taxane-induced neuropathy was performed using iPLEX Gold method. Risk allele carrier frequencies of 19 SNPs that passed quality checks were compared between those with/without high CIPN symptoms using logistic regression, adjusting for age. Receiver operating characteristic (ROC) curves using clinical risk factors (age, diabetes, BMI, Charlson Comorbidity Index, previous cancer diagnosis) with and without the identified SNPs were compared. RESULTS: 107 individuals received platinum or taxane-based chemotherapy and provided sufficient DNA for analysis. Median age was 65.1 years; 39.6% had obesity and 8.4% diabetes; most had ovarian (58.9%) or uterine cancer (29.0%). Two SNPs were significantly associated with high CIPN symptomatology: rs3753753 in GPX7, OR = 2.55 (1.13, 5.72) and rs139887 in SOX10, 2.66 (1.18, 6.00). Including these two SNPs in a model with clinical characteristics led to an improved AUC for CIPN symptomatology (0.65 vs. 0.74, p = 0.04). CONCLUSIONS: Genetic and clinical characteristics were predictive of higher CIPN symptomatology in gynecologic cancer survivors, and combining these factors resulted in superior predictive power compared with a model with clinical factors only. Prospective validation and assessment of clinical utility are warranted.

Cytomegalovirus and systemic inflammation at time of surgery is associated with worse outcomes in serous ovarian cancer.

OBJECTIVES: Cytomegalovirus (CMV) is a common infection that establishes latency in healthy people. CMV has been associated with alterations of the immune compartment leading to improved responses, while inflammation has been shown to adversely impact outcomes. We investigated whether CMV serostatus predicts outcomes in ovarian cancer in the presence or absence of inflammation. METHODS: A total of 106 patients with serous ovarian cancer from 2006 to 2009 were analyzed. CMV and systemic inflammation was measured using CMV immunoglobulin G (IgG) and C-reactive protein (CRP), respectively, in serum collected prior to cytoreduction. Patients were stratified by CMV IgG (non-reactive, reactive/borderline) and CRP (≤10, >10 mg/L) status. Overall survival (OS) and recurrence-free survival (RFS) were compared by group using log-rank tests and Cox proportional hazards regression models adjusting for age at surgery. RESULTS: Of 106 eligible patients, 40 (37.7%) were CMV+/CRP+, 24 (22.6%) CMV+/CRP-, 19 (17.9%) CMV-/CRP+, and 23 (21.7%) CMV-/CRP-. CRP+ had higher CA-125 levels (P = 0.05) and higher rates of suboptimal debulking (P = 0.03). There were no other significant differences in demographic, surgical, or pathologic factors between groups. CMV+/CRP+ patients median RFS and OS were 16.9 months (95% CI: 9.0-21.1) and 31.7 months (95% CI: 25.0-48.7), respectively, with a significantly worse RFS (aHR: 1.85, 95% CI: 1.05-3.24, P = 0.03) and OS (aHR: 2.12, 95% CI: 1.17-3.82, P = 0.01) compared to CMV-/CRP- (RFS = 31.2 months (95% CI: 16.0-56.4) and OS = 63.8 months (95% CI: 50.7-87.0)). CMV+/CRP- group displayed the longest OS (89.3 months). CONCLUSIONS: Previous exposure to CMV and high CRP at surgery portended worse RFS and OS compared to women who tested negative. The CMV+/CRP- group had the longest OS, indicating that CMV status alone, in the absence of inflammation, may be protective.