High-volume ovarian cancer care: Survival impact and disparities in access for advanced-stage disease

Objective

To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers.

Methods

Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96–12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥ 20 cases/year), high-volume physicians (HVP) (≥ 10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables.

Results

A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16–1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22–2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07–2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46–4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90–4.23).

Conclusions

Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities.     

Outcomes of ovarian preservation in a cohort of premenopausal women with early-stage endometrial cancer: A Korean Gynecologic Oncology Group study

Objective

The aim of this study was to evaluate the impact of ovarian preservation on the recurrence and survival rates of premenopausal women with early-stage endometrial cancer.

Methods

Using medical records of premenopausal women who received primary surgical treatment for stage I–II endometrial cancer, the demographics and survival rates were compared retrospectively for patients who had ovarian preservation and those who underwent bilateral salpingo-oophorectomy. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) based on propensity score were performed to adjust for selection bias between the two groups.

Results

A total of 495 women were identified, including 176 patients who had ovarian preservation. The ovarian preservation group was younger (P < 0.001) and had an earlier year of diagnosis (P = 0.014), a lower prevalence of lymphadenectomy (P < 0.001), and a marginally significant association with lower tumor grade (P = 0.052). The Kaplan–Meier curve and the log rank test showed no difference in either recurrence-free survival (P = 0.742) or overall survival (P = 0.462) between the two groups. In a multivariate Cox model adjusted by IPTW and covariates, ovarian preservation had no effect on either recurrence (hazard ratio [HR], 0.73; 95% CI, 0.29–1.81) or overall survival (HR, 1.33; 95% CI, 0.43–4.09).

Conclusions

Ovarian preservation does not appear to be associated with an adverse impact on the outcomes of premenopausal women with early-stage endometrial cancer. The present study has useful implications for physicians counseling young women who want to preserve their ovaries.     

Spatial analysis of adherence to treatment guidelines for advanced-stage ovarian cancer and the impact of race and socioeconomic status

Objective

To determine the impact of geographic location on advanced-stage ovarian cancer care adherence to the National Comprehensive Cancer Network (NCCN) guidelines in relation to race and socioeconomic status (SES).

Methods

Patients diagnosed with stage IIIC/IV epithelial ovarian cancer (1/1/96–12/31/06) were identified from the California Cancer Registry. Generalized additive models were created to assess the effect of spatial distributions of geographic location, proximity to a high-volume hospital (≥ 20 cases/year), distance traveled to receive care, race, and SES on adherence to NCCN guidelines, with simultaneous smoothing of geographic location and adjustment for confounding variables. Disparities in geographic predictors of treatment adherence were analyzed with the x² test for equality of proportions.

Results

Of the 11,770 patients identified, 45.4% were treated according to NCCN guidelines. Black race (OR = 1.49, 95%CI = 1.21–1.83), low-SES (OR = 1.46, 95%CI = 1.24–1.72), and geographic location ≥ 80 km/50 mi from a high-volume hospital (OR = 1.88, 95%CI = 1.61–2.19) were independently associated with an increased risk of non-adherent care, while high-volume hospital treatment (OR = 0.59, 95%CI = 0.53–0.66) and travel distance to receive care ≥ 32 km/20 mi (OR = 0.80, 95%CI = 0.69–0.92) were independently protective. SES was inversely associated with location ≥ 80 km/50 mi from a high-volume hospital, ranging from 6.3% (high-SES) to 33.0% (low-SES) (p < 0.0001). White patients were significantly more likely to travel ≥ 32 km/20 mi to receive care (21.8%) compared to Blacks (14.4%), Hispanics (15.9%), and Asian/Pacific Islanders (15.5%) (p < 0.0001).

Conclusion

Geographic proximity to a high-volume hospital and travel distance to receive treatment are independently associated with NCCN guideline adherent care for advanced-stage ovarian cancer. Geographic barriers to standard ovarian cancer treatment disproportionately affect racial minorities and women of low-SES.     

Synchronous primary cancers of the endometrium and ovary in young women: A Korean Gynecologic Oncology Group Study

Objective

Some authors have recommended the use of diagnostic laparoscopy as a pretreatment assessment step for conservative hormonal treatment in young women with endometrial cancer. The aim of this study was to determine the incidence of synchronous primary cancer of the endometrium and ovary in young women.

Methods

The medical records of 3240 patients with endometrial cancer who underwent primary surgery between 1995 and 2010 were collected from 7 institutions and were retrospectively reviewed. Low-risk endometrial cancer was defined as tumors without myometrial invasion; normal or benign-looking ovaries; normal CA-125; grade 1 endometrioid histology; and early stage endometrial cancer on pretreatment assessment.

Results

Fifteen percent (471/3240) were younger than 40 years of age. The incidence of synchronous ovarian cancer in young women with endometrial cancer was 4.5% (21/471). In patients with low-risk endometrial cancer, synchronous cancers were not identified.

Conclusion

The incidence of synchronous ovarian malignancies in young women with endometrial cancer was quiet low (4.5%), unlike previous studies have revealed (11–29%). Therefore, diagnostic laparoscopy is not mandatory in patients with low-risk early stage endometrial cancer selected for conservative treatment to confirm the absence of ovarian malignancy.     

Racial disparities and patterns of ovarian cancer surgical care in California

Objective

To investigate disparities in the frequency of ovarian cancer-related surgical procedures and access to high-volume surgical providers among women undergoing initial surgery for ovarian cancer according to race.

Methods

The California Office of Statewide Health Planning and Development database was accessed for women undergoing a surgical procedure that included oophorectomy for a malignant ovarian neoplasm between 1/1/06 and 12/31/10. Multivariate logistic regression analyses were used to evaluate differences in the odds of selected surgical procedures and access to high-volume centers (hospitals ≥ 20 cases/year) according to racial classification.

Results

A total of 7933 patients were identified: White = 5095 (64.2%), Black = 290 (3.7%), Hispanic/Latino =1400 (17.7%), Asian/Pacific Islander = 836 (10.5%) and other = 312 (3.9%). White patients served as reference for all comparisons. All minority groups were significantly younger (Black mean age 57.7 years, Hispanic 53.2 years, Asian 54.5 years vs. 61.1 years, p < 0.01). Hispanic patients had lower odds of obtaining care at a high-volume center (adjusted OR (adj. OR) = 0.72, 95% CI = 0.64–0.82, p < 0.01) and a lower likelihood of lymphadenectomy (adj. OR = 0.80, 95% CI = 0.70–0.91, p < 0.01), bowel resection (adj. OR = 0.80, 95% CI = 0.71–0.91, p < 0.01), and peritoneal biopsy/omentectomy (adj. OR = 0.69, 95% CI = 0.58–0.82, p < 0.01). Black racial classification was associated with a lower likelihood of lymphadenectomy (adj. OR = 0.76, 95% CI = 0.59–0.97, p = 0.03).

Conclusions

Among women undergoing initial surgery for ovarian cancer, Hispanic patients are significantly less likely to be operated on at a high-volume center, and both Black and Hispanic patients are significantly less likely to undergo important ovarian cancer-specific surgical procedures compared to White patients.     

The occurrence of endometriosis with ovarian carcinomas is not purely coincidental

Objective

To explore the association between epithelial ovarian cancer (EOC) and common benign gynecological disorders.

Study design

The medical records of 226 patients with EOC treated at Peking Union Medical College Hospital between March 2011 and March 2012 were reviewed. Histological evaluations had been performed to determine the presence of coexisting pelvic endometriosis (n = 17), uterine leiomyoma (n = 66), adenomyosis (n = 22), or endometrial polyps (n = 17).

Results

Coexistence of endometriosis occurred in 35.3% and 36.4% of cases of the clear cell and endometrioid subtypes of EOC histology, respectively. Endometriosis was more likely associated with clear cell or endometrioid ovarian carcinoma, but less likely with high grade serous cancer. No differences were observed in the concurrence of uterine myoma, adenomyosis or endometrial polyps among the different subtypes of EOC.

Conclusions

In contrast to other common benign gynecological disorders, endometriosis showed close relationships with the clear cell and endometrioid subtypes of EOC specifically.     

Characteristics of clear cell ovarian cancer arising from endometriosis: A two center cohort study

Objective

Endometrioid and clear cell ovarian tumors have been referred to as “endometriosis associated ovarian cancers”. However, very few studies have compared clinical and prognostic features of endometriosis-associated cancers or cancers not associated with endometriosis according to specific histotypes. We have investigated clinical and histological features of the largest published series of clear cell ovarian cancers arising in endometriosis using a retrospective database.

Methods

Seventy three patients with a primary diagnosis of either pure clear cell ovarian cancer and mixed endometrioid-clear cell ovarian cancer have been divided into two groups according to the detection of cancer strictly arising from ovarian endometriosis or not (n = 27 and n = 46, respectively). Clinical and pathological data have been compared.

Results

Patients with clear cell carcinomas arising from endometriosis tend to be significantly younger (51.4 ± 10.0 and 58.4 ± 11.2 years, p = 0.02). FIGO stage, laterality, prevalence of pure versus mixed histology, and presence of synchronous endometrial carcinoma were not significantly different between the two groups. Unilateral ovarian involvement was more frequent in cases arising in endometriosis (85% vs 63%, p = 0.04). Ascites was not found in any of the endometriosis-associated cancer cases vs 19.5% in patients without endometriosis. The presence of endometriosis did not affect 5-year overall survival rates.

Conclusions

Endometriosis per se does not appear to be associated with a lower stage tumor or to predict prognosis in ovarian clear cell cancers. Unilateral involvement and reduced presence of ascites may be linked to the cystic nature of endometriosis which frequently presents as monolateral and in which associated tumors are more likely to be longer confined to the ovary before spreading.     

The results of gynecologic surveillance in families with hereditary nonpolyposis colorectal cancer

Objective

We aimed to estimate the incidence rate of endometrial cancer (EC) and to evaluate the results of EC-surveillance in hereditary nonpolyposis colorectal cancer (HNPCC) families.

Methods

All at-risk women recommended for EC-surveillance by the HNPCC-register—2959 women (19,334 women years)—were included. Data on EC-surveillance were available for 871 women (6894 women years), who had performed 1945 surveillance visits. The average surveillance period was 7.9 (range 0.1−21.7) years and 46% of the women had had less than 3 years between their visits.

Results

During 19,334 women years, 60 women with gynecological malignancies or premalignancies were diagnosed. Thirty-nine women had EC. Of these, 31 were from families with identified MMR gene mutations with the median age at diagnosis of 54 (39–83) years (Incidence Rate, IR = 0.63 per 100 women years) and four women from each Amsterdam (AMS)-positive and AMS-like families (median age 64 (55–73) years, IR = 0.06 and 0.05 per 100 women years, respectively, p < .0001).Among the 871 surveilled women, 13 EC were found: 7/13 cases were diagnosed by surveillance examination—two as prevalent cancers, diagnosed at the first visit—and 6/13 based on symptoms. In addition, five complex atypical hyperplasias and four ovarian cancers (OCs) were diagnosed. All these women were MMR mutation carriers.

Conclusion

Based on 19,334 women years of EC-surveillance, our analysis provides a thorough estimation of the EC risk in women with an MMR mutation, or suspected of having Lynch syndrome. We conclude that EC surveillance should only be targeted at MMR-mutation carriers.     

The value of imaging of the lungs in the diagnostic workup of patients with endometrial cancer

Objective

Imaging of the lungs is part of the routine diagnostic workup of patients with endometrial cancer. The present study aimed to determine the incidence of lung metastases in patients with endometrial cancer and to evaluate the clinical relevance of preoperative chest imaging in this population.

Methods

A retrospective cross-sectional study was performed in four regional and one university hospital in the southeastern part of the Netherlands. A total of 784 patients with epithelial endometrial cancer diagnosed between 2002 and 2010 in five hospitals were included. Patients were followed up for at least 1 year.

Results

Of 784 patients, 541 (69.0%) underwent thoracic imaging and 11 showed findings suspicious for metastases perioperatively or during the 1-year follow-up period. In eight patients, the thoracic metastases were related to their endometrial cancer, resulting in an overall incidence of 1.0% (8/784, 95% CI = 0.3–1.7%). These eight patients had high-risk subtypes of endometrial cancer (serous, clear cell or poorly differentiated endometrioid), and the incidence was 4.1% (8/193, 95% CI = 1.9–8.3%) for these subtypes. Lung metastases were not detected in any of the patients with low-risk subtypes of endometrial cancer (n = 566) at the time of diagnosis (95% CI = 0–0.8%).

Conclusions

The probability of detecting thoracic metastases during the diagnostic workup of patients with endometrial cancer is low. The present data suggest that thoracic imaging could be omitted from the diagnostic workup of patients with low-risk endometrial cancer.     

The influence of comorbidity on mortality in ovarian cancer patients

Background

Ovarian cancer is a severe disease with a peak incidence in the older age groups where concurrent morbidity is common and could potentially influence mortality rates.

Objectives

The aim was to study the influence of common comorbidity diagnoses on mortality in ovarian cancer patients.

Methods

The study population was patients with ovarian cancer in Sweden 1993–2006 (n = 11.139) identified in the national Cancer Register. Comorbidity data was obtained from the Patient Register and mortality from Cause of Death Register. Mortality was analyzed with Cox' proportional hazards models and subgroup analyses were performed by age and tumor histology.

Results

Almost all of the assessed comorbidities increased mortality in ovarian cancer patients. Thromboembolism was the most hazardous comorbidity (HR = 1.95, < 1 year after cancer diagnosis and HR = 7.83, 1–5 years after cancer diagnosis) followed by hematologic complications (HR = 1.84 and 7.11 respectively) and infectious disease (HR = 1.48 and 5.28 respectively). The occurrence of diabetes mellitus and hypertension had less impact on mortality.

Conclusion

Thromboembolism, hematologic complications and infections had a pronounced effect on mortality rates in women with ovarian cancer. The impact of comorbidity was mainly apparent among those with a more prosperous prognosis, such as longer time since cancer diagnosis, less aggressive tumors and younger age.     

Statins,aspirin and risk of thromboembolic events in ovarian cancer patients

Objectives

Studies suggest that statins and low dose aspirin reduce risk of VTEs in the general population. We aimed to study the effect of these drugs on the incidence of VTEs in patients with ovarian cancer.

Methods

Patients diagnosed with ovarian cancer between 2000 and 2011 were identified through the Clalit Health Services (CHS) chronic disease registry. Data were extracted from CHS database and from computerized pharmacy records. Use of medications was analyzed as a time dependent covariate in a Cox regression model.

Results

Of 1746 patients 175 (10%) had a VTE during a median follow up of 3.13 years. 83 patients (5.6%) had a VTE within 2 years of diagnosis of ovarian cancer. Use of chemotherapy and stage 3 and 4 at presentation were associated with an increased risk for VTEs.Statins were used by 43.5% of the patients, and 32.3% used aspirin. Aspirin use was associated with a marginally significant reduction in incidence of VTEs within 2 years of diagnosis, HR 0.423 (95% CI 0.182–1.012, p-value 0.053). Statin use was not associated with risk of VTEs.

Conclusion

This is the first study looking at the effect of statins and aspirin on the incidence of VTEs in ovarian cancer patients. In our cohort, statins did not decrease the risk for a VTE and aspirin use was associated with a reduced risk which was marginally significant. Our results might be explained by use of low potency statins and by alternate mechanisms for VTE formation in cancer patients.     

A large scale population-based cohort study on the risk of ovarian neoplasm in patients with type 2 diabetes mellitus

Objective

To investigate whether the risk of developing ovarian cancer is elevated in women with diabetes mellitus.

Methods

The study is a population-based cohort study. Women with type 2 diabetes (n = 319,310) and age-matched controls (n = 319,308) were selected from the ambulatory care claims and beneficiary registry in 2000, respectively. Selected patients were linked to the in-patient claims (2000–2008) to identify admissions due to ovarian (ICD-9-CM: 183.xx) cancer. The person-year approach with Poisson assumption was used to estimate the incidence density rate. The age-specific hazard ratios (HRs) of ovarian cancer in relation to diabetes were calculated using multivariate Cox proportional hazard regression model.

Results

The overall incidence density rate of ovarian cancer was estimated at 1.87 (95% confidence interval (CI) 1.70–2.05) per 10,000 patient-years for patients with diabetes. The corresponding figures for controls were slightly lower at 1.79 per 10,000 patient-years. The incidence density of ovarian cancer was increased with age in diabetes but not in controls. The covariate-adjusted HR for ovarian cancer was statistically compared with null (adjusted HR = 1.06, 95% CI = 0.92–1.22) in women with diabetes. Moderately elevated HR was noted in women with diabetes aged < 50 (adjusted HR = 1.17, 95% CI = 0.82–1.65) and in women with diabetes aged > 65 (adjusted HR = 1.10, 95% CI = 0.92–1.42). The null association between diabetes and ovarian cancer remains true regardless of the disease duration of diabetes.

Conclusion

This large-scale cohort study provides little support on the putative association between type 2 diabetes and the risk of ovarian cancer.     

Applicability of the concept of “platinum sensitivity” to recurrent endometrial cancer: The SGSG-012/GOTIC-004/Intergroup study

Objective

The concept of “platinum sensitivity” has been widely applied in the management of recurrent ovarian cancer. This study aimed to evaluate the applicability of this concept to recurrent endometrial cancer.

Patients and methods

In this multicenter retrospective cohort study, the clinical data of patients with recurrent endometrial cancer, who had a history of receiving first-line platinum-based chemotherapy and who received second-line platinum-based chemotherapy at the time of recurrence between January 2005 and December 2009 were reviewed.

Results

A total of 262 patients from 30 centers with initial FIGO stage classifications of I (29), II (23), III (122), and IV (88) were enrolled. In total, 153 endometrioid adenocarcinomas, 34 serous adenocarcinomas, 17 clear cell adenocarcinomas, 36 carcinosarcomas, and 22 “other” tumors were documented. The response rates for patients with platinum-free intervals of < 6 months, 6–11 months, 12–23 months, and ≥ 24 months were 25%, 38%, 61%, and 65%, respectively. The median progression-free survival after second-line platinum-based chemotherapy for patients with platinum-free intervals of < 12 months and ≥ 12 months was 4.4 (95% confidence interval (CI) = 3.7–5.8) months and 10.3 (95% CI = 8.2–12.6) months, respectively (log-rank P < 0.0001), and the median overall survival was 13.8 (95% CI = 10.6–18.1) months and 40.9 (95% CI = 25.3–54.2) months, respectively (log-rank P < 0.0001).

Conclusion

Platinum-free interval is a predictor of response and survival after second-line platinum-based chemotherapy in patients with recurrent endometrial cancer. The concept of “platinum sensitivity” could be applicable to recurrent endometrial cancer.     

Metformin is associated with improved survival in endometrial cancer

Objective

Preclinical evidence suggests that metformin exhibits anti-tumorigenic effects in endometrial cancer. We sought to investigate the association of metformin on endometrial cancer outcomes.

Methods

A multi-institutional IRB-approved retrospective cohort analysis was conducted comparing endometrial cancer patients with diabetes mellitus who used metformin (based on medication review at the time of diagnosis) to those who did not use metformin from 2005 to 2010. Metformin use on treatment related outcomes (TTR: time to recurrence; RFS: recurrence free survival; OS: overall survival) were evaluated using univariate and multivariate modeling.

Results

24% (363/1495) endometrial cancer patients were diabetic, of whom 54% used metformin. Metformin users were younger and heavier than non-users, though nearly all were postmenopausal and obese. 75% of both groups had endometrioid histology. Stage, grade, and adjuvant therapy distributions were similar. Metformin users had improved RFS and OS. Non-metformin users had 1.8 times worse RFS (95% CI: 1.1–2.9, p = 0.02) and 2.3 times worse OS (95% CI: 1.3–4.2, p = 0.005) after adjusting for age, stage, grade, histology and adjuvant treatment. Metformin use was not associated with TTR.

Conclusion

Metformin use was associated with improved RFS and OS but not TTR, most likely due to improving all-cause mortality. Its role in modifying cancer recurrence remains unclear. Prospective studies that capture metformin exposure prior to, during and post endometrial cancer treatment may help define the role of metformin upon cancer specific and overall health outcomes.     

Metformin use and endometrial cancer survival

Objective

Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancers using metformin has been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC).

Methods

We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan–Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided.

Results

Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p = 0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p < 0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and the presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed.

Conclusion

Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC.     

Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?

Objective

To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer.

Methods

We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan–Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer.

Results

A total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70 years was estimated to be 0.94% (95% CI 0.83–1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75–4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63–5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age < 50 years (HR 1.48, 95% CI 1.15–1.91).

Conclusion

An increased risk of endometrial cancer is associated with a family history of endometrial cancer or early-onset colorectal cancer for women without a MMR gene mutation, indicating for potential underlying genetic and environmental factors shared by colorectal and endometrial cancers other than caused by MMR gene mutations.     

Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate,Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

Objective

Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers.

Methods

We conducted a nested case–control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates.

Results

Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06–3.93), p-trend = 0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14–4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06–4.63), p-trend = 0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96–3.61), p-trend = 0.05]. In analyses restricted to serous ovarian cancer (n = 83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14–11.14), p-trend = 0.008; IL-8 T3 vs. T1: 3.05 (1.09–8.51), p-trend = 0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis (n = 56).

Conclusion

These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.     

Prevalence of Human Papillomavirus in endometrial cancer: A systematic review and meta-analysis

Objective

HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.

Methods

We conducted a systematic review and meta-analysis to investigate the pooled prevalence of HPV DNA in endometrial cancer. Using meta-regression, we further analyzed whether factors such as geographical region, HPV DNA detection method, publication year and tissue type were associated with HPV prevalence. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for studies providing data on HPV prevalence in cases with endometrial cancer and in controls with normal or hyperplastic endometrial tissue.

Results

We identified 28 papers (29 studies) examining the prevalence of HPV DNA in tumor tissue from endometrial cancer comprising altogether 1026 cases of endometrial cancer. The HPV prevalence varied considerably from 0% to 61.1%. From the random effects meta-analysis, the pooled prevalence of HPV DNA in endometrial cancer was 10.0% (95% CI: 5.2–16.2) with large between-study heterogeneity (I² = 88.2%, p < 0.0001). The meta-regression showed that HPV DNA detection method was statistically significantly associated with HPV prevalence (p = 0.0016): the pooled HPV prevalence was 6.0% (95% CI: 1.5–13.0) using general primers, 18.9% (95% CI: 8.6–32.1) using type-specific primers and 1.0% (95% CI: 0.0–3.6) using non-PCR based methods. None of the other a priori defined variables were statistically significantly associated with HPV prevalence. The pooled OR was 1.43 (95% CI: 0.68–3.00) indicating that the odds of HPV was not increased in cases versus controls.

Conclusions

HPV appears to have a limited or no role in the etiology of endometrial cancer.     

A genetic variant in pre-miR-27a is associated with a reduced cervical cancer risk in southern Chinese women

Objective

MicroRNAs (miRNAs) play critical roles in cervical carcinogenesis. Common single nucleotide polymorphisms (SNPs) in pre/pri-miRNAs may change their property through altering miRNAs expression and/or maturation. Here we aimed to investigate the influence of three common SNPs in pre/pri-miRNAs (pri-miR-26a-1 rs7372209, pre-miR-27a rs895819 and pri-miR-100 rs1834306) on individual susceptibility to cervical cancer.

Methods

We genotyped these three polymorphisms in 103 cervical cancer cases and 417 cancer-free female subjects using polymerase chain reaction–ligation detection reaction (PCR–LDR) method. Unconditional logistic regression analysis was utilized to estimate the association between these polymorphisms and the risk of cervical cancer.

Results

In a logistic regression analysis, we found that the rs895819 polymorphism in pre-miR-27a exhibited a significant effect on cervical cancer risk; T allele (OR = 0.68, 95% CI = 0.49–0.95, P = 0.025), and CT (OR = 0.33, 95% CI = 0.15–0.74, P = 0.007) or TT (OR = 0.33, 95% CI = 0.15–0.72, P = 0.006) genotype were associated with the decreased risk, compared to C and CC respectively. As we used further genotype association models, we found a similar trend of the association in additive (OR = 0.70, P = 0.041) and recessive model (OR = 0.33, P = 0.004). We did not detect any association of the other two SNPs in pri-miR-26a-1 (rs7372209) and pri-miR-100 (rs1834306) with cervical cancer risk.

Conclusion

Our study provides the first evidence that the miR-27a rs895819 polymorphism is associated with a decreased risk of cervical cancer in southern Chinese women.     

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Objective

Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma.

Methods

Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I–IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes.

Results

LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r = 0.31, p = 0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93–20.4, p = 0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p = 0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54–5.88, p = 0.001) and overall survival (HR 2.69, 95%CI 1.18–6.23, p = 0.021) while ER-expression did not remain as a significant variable in multivariate analysis.

Conclusion

Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.