Does the use of low-molecular-weight heparin during pregnancy change the expression of PD-1 and PDL-1 in women with recurrent pregnancy loss?

Objective: The programed cell death gene-1 ligand (PDL-1) is expressed by villous syncytiotrophoblasts, cytotrophoblasts, and fetal cells in close contact with maternal tissue and blood. Programmed cell death gene-1 (PD-1) and the PDL-1 pathway cooperate with human leucocyte antigen-G (HLA-G), expressing intermediate trophoblastic cells and syncytiotrophoblasts to inhibit the function of activated T-cells. With this mechanism, the immunosuppressive microenvironment protects the placenta. This study investigated changes in PD-1 and PD-L1 gene expression in patients with a history of recurrent pregnancy loss (RPL). Materials and Methods: Sixty patients participated in the study and were divided into three groups. Group 1 (G1): healthy pregnancy, G2: RPL but not low-molecular-weight heparin (LMWH), and G3: RPL and LMWH. PD-1 gene expression in placental tissue samples was measured by reverse-transcriptase polymerase chain reaction and PD-L1 Elisa assay, and the study was supported by histopathology. Results: The PD-L1 value decreased significantly in G2. A significant difference was observed between the groups in PD-1 gene expression levels in G1 and G2. It was observed that vascularization increased and the villi structures intensified in G3. In G2, there was villus dysplasia in the placenta, enlargement in the intervillous region, and fibrin deposition. It was observed that the villi structures in G3 returned to a morphology similar to that of G1. Conclusion: T-cells are activated in patients using LMWH, and a new therapeutic strategy can be developed to prevent pregnancy loss by targeting the PD-1 pathway.

Endocervical polyps in high risk human papillomavirus infections.

OBJECTIVES: Human papillomavirus (HPV) positive patients with and without endocervical polyps is compared with respect to HPV genotypes and presence of pre-invasive diseases. To our knowledge, this is the first and largest report in the literature examining the endocervical polyps in HPV positive cases. MATERIAL AND METHODS: Clinicopathological data for the first one million screening patients (n = 1060 992) from around the entire country during 2015 and 2016 were targeted for this research. Colposcopy, colposcopic surgical diagnostic procedures and final pathology results of 3499 patients with high-risk (HR) HPV-positive were obtained from reference colposcopy centers. Patients with endocervical polyps (n = 243 [6.9 %]) were accepted as experimental arm while patients without any endocervical polyp (n = 3256 [93.1%]) were regarded as the control group. Age, HPV genotype, Pap smear abnormality, and final pathological results were compared between two groups using Student's t-test and cross-tabulation chi-square test. RESULTS: The incidence of endocervical polyp was found to be 6.9 % in HR HPV-positive women. The most common HPV genotypes observed in both groups were HPV 16 or 18. Abnormal cytology reports (≥ ASC-US) were not significantly different between both groups. However, with respect to final pathological diagnosis, patients with endocervical polyp had significantly lower numbers of pre-invasive diseases (31.3% vs 44.2%; p < 0.10). CONCLUSIONS: Endocervical polyps may be more common in patients with HR HPV infections. HPV 18 is observed significantly more, in the HR HPV positive endocervical polyp group. Patients with endocervical polyps do not have increased risk for preinvasive cervical diseases.

Factors affecting parametrial involvement in cervical cancer patients with tumor size ≤4 cm and selection of low-risk patient group

Objective: The primary aim of this study was to evaluate the factors affecting parametrial involvement in cervical cancer patients with tumor size ≤4 cm and selection of the low-risk patient group based on long-term oncologic outcomes. Material and Methods: Cervical cancer patients operated in the gynecologic oncology division between 2007 and 2013 were retrospectively evaluated. One-hundred and sixty-eight patients with tumor size ≤4 cm were identified. Of these, 159 (86.8%) underwent radical hysterectomy plus pelvic-para-aortic lymphadenectomy and nine (13.2%) underwent fertility-sparing surgery [radical trachelectomy (n=7); large conization (n=2)]. Factors affecting parametrial invasion, including lymphovascular space invasion (LVSI), deep stromal invasion (DSI), lymph node metastases, and tumor size, were evaluated. Statistical analyses were performed using SPSS 23.0 (IBM Corp., Armonk, NY, USA). Results: Median age was 49.5 years and median tumor size was 2.5 cm (0.45-4 cm). In both univariate and multivariate analyses, the risk of parametrial involvement was increased with LVSI with a hazard ratio (HR) of 3.45 [95% confidence interval (CI): 1.1-10.8] and DSI with a HR of 4.1 (95% CI: 1.18-14.8), while tumor size of ≤2 cm was only significant in univariate analyses. Furthermore, 26 early-stage patients were identified with low-risk factors and they had no parametrial involvement, lymph node metastases, recurrence, or death from disease over 77 months. Conclusion: Parametrial involvement in low-risk cervical cancer is very rare and less radical procedures may be safe in these patients.

Relationship between contraceptive methods and human papillomavirus positivity.

PURPOSE: Understanding the effect of contraceptive use on high-risk human papillomavirus (HPV) positivity may provide information that is valuable to women in contraceptive decision-making. This study includes women aged 30-65 years who admitted to Family Planing outpatient clinic and have hrHPVDNA positivity. METHODS: We included a total of 801 women. All participants underwent national cervical cancer screening using HPV screening test conducted by the Cancer Control Department of the Ministry of Health. They completed a questionnaire on demographic information and potential risk factors. RESULTS: The HPV DNA positivity rate among all participants was 8.4%. The two most common HPV genotypes were HPV16 and HPV51. Meanwhile, hrHPV infection was associated with age, marital status, smoking status, and contraceptive method. CONCLUSION: HPV is the most common cause of sexually transmitted diseases. Understanding about the reproductive and demographic characteristics affecting HPV persistence is crucial. The effect of contraceptive methods on HPV positivity is important information that is necessary to be relayed to women by healthcare professionals.

Mega Hpv laboratories for cervical cancer control: Challenges and recommendations from a case study of Turkey.

Cervical cancer is the fourth most common cancer among women in the world. It is estimated that one woman dies every 2 min from cervical cancer. Nearly all cervical cancers are preventable by early detection and treatment through screening or HPV vaccination. In 2018, World Health Organization (WHO) made a global call for action toward the elimination of cervical cancer. Cervical cancer screening involves a complex organized program, which begins with a call/recall system based on personal invitation of eligible women, followed by participation in screening, and leading to diagnosis, treatment, and management as appropriate. An effective cervical screening program with high coverage is dependent on each country's infrastructure and human resource capacity. Efforts to develop an effective program is particularly challenging in low and middle income countries (LMIC) where resources are limited. For an effective strategy, Turkey redesigned the country's cervical screening program. The local call/recall system and centralized monitoring system of individual women were re-vamped with an automated evaluation system. The revised screening program includes the use of primary HPV testing with a well-defined protocol outlining the algorithms of management (i.e., screening intervals and referral), a single nationwide centralized diagnostic laboratory, and a sustainable agreement with the HPV diagnostics industry. This system allows for traceable, real-time monitoring of screening visits and specimens. Turkey reports on the first four years of this re-vamped organized program and shares lessons learnt from the implementation of this new program.

A novel prediction method for lymph node involvement in endometrial cancer: machine learning.

OBJECTIVE: The necessity of lymphadenectomy and the prediction of lymph node involvement (LNI) in endometrial cancer (EC) have been hotly-debated questions in recent years. Machine learning is a broad field that can produce results and estimations. In this study we constructed prediction models for EC patients using the Naïve Bayes machine learning algorithm for LNI prediction. METHODS: The study assessed 762 patients with EC. Algorithm models were based on the following histopathological factors: V1: final histology; V2: presence of lymphovascular space invasion (LVSI); V3: grade; V4: tumor diameter; V5: depth of myometrial invasion (MI); V6: cervical glandular stromal invasion (CGSI); V7: tubal or ovarian involvement; and V8: pelvic LNI. Logistic regression analysis was also used to evaluate the independent factors affecting LNI. RESULTS: The mean age of patients was 59.1 years. LNI was detected in 102 (13.4%) patients. Para-aortic LNI (PaLNI) was detected in 54 (7.1%) patients, of which four patients had isolated PaLNI. The accuracy rate of the algorithm models was found to be between 84.2% and 88.9% and 85.0% and 97.6% for LNI and PaLNI, respectively. In multivariate analysis, the histologic type, LVSI, depth of MI, and CGSI were independently and significantly associated with LNI (p<0.001 for all). CONCLUSIONS: Machine learning may have a place in the decision tree for the management of EC. This is a preliminary report about the use of a new statistical technique. Larger studies with the addition of sentinel lymph node status, laboratory findings, or imaging results with machine learning algorithms may herald a new era in the management of EC.

Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women.

To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 1 million screened women. Women over age 30 were invited for population based screening via HPV DNA and conventional cytology. Samples were collected by family physicians and the evaluations and reports had been performed in the National Central HPV laboratories. The acceptance rate for HPV based cervical cancer screening after first invitation was nearly 36.5%. Since HPV DNA tests have been implemented, cervical cancer screening rates have shown 4-5-fold increase in primary level. Through the evaluation of all, HPV positivity was seen in 3.5%. The commonest HPV genotypes were 16, followed by 51, 31, 52 and 18. Among the 37.515 HPV positive cases, cytological abnormality rate was 19.1%. Among HPV positive cases, 16.962 cases had HPV 16 or 18 or other oncogenic HPV types with abnormal cytology (>ASC-US). These patients were referred to colposcopy. The colposcopy referral rate was 1.6%. Among these, final clinico-pathological data of 3.499 patients were normal in 1.985 patients, CIN1 in 708, CIN2 in 285, CIN3 in 436 and cancer in 85 patients and only pap-smear program could miss 45.9% of ≥CIN3 cases. The results of 1 million women including the evaluation of 13 HPV genotypes with respect to prevalence, geographic distribution and abnormal cytology results shows that HPV DNA can be used in primary level settings to have a high coverage rated screening program and is very effective compared to conventional pap-smear.

Survival of gynecological cancers in Turkey: where are we at?

OBJECTIVE: To investigate the 5-year relative survival rates in gynecological cancers diagnosed and treated in Turkey by year 2009 and to compare the results with developed countries. METHODS: Data of patients diagnosed for ovarian, corpus uteri or cervix uteri cancer at year 2009 are collected from 9 national cancer registry centers. Date of deaths are retracted from governmental Identity Information Sharing System (KPS). In order to calculate relative survival rates, national general population mortality tables are obtained from Turkish Statistical Institute (TurkStat). Hakulinen method is used for computing curves by R program. Data for European, Asian and some developed countries were obtained from official web pages. RESULTS: A total of 1,553 patients are evaluated. Among these, 713 (45.9%) are corpus uteri cancers, while remaining 489 (31.5%) are ovarian and 351 (22.6%) are cervix uteri. Five-year overall relative survival rates are 85%, 50%, and 62% for corpus uteri, ovarian, and cervix uteri, respectively. These figures are between 73%-87% for corpus uteri, 31%-62% for ovarian and 61%-80% for cervix uteri in developed countries. Stage is the most important factor for survival in all cancers. Five-year relative survival rates in corpus uteri cancers are 92%, 66%, and 38% for localized, regional, and distant metastatic disease, respectively. These figures are 77%, 57%, and 29% for ovarian; 80%, 50%, and 22% for cervix uteri. CONCLUSION: This is the first report from Turkey giving national overall relative survival for gynecological cancers from a population based cancer registry system.

Trends of Gynecological Cancers in Turkey: Toward Europe or Asia?

OBJECTIVE: The aim of this study was to evaluate nationwide gynecological cancer trends in Turkey. METHODS: National cancer registry data (2009-2013) of Turkish Ministry of Health were evaluated. Ovarian, cervical, endometrial, vulvar, vaginal, and tubal cancers are evaluated with respect to age of diagnosis, incidence rates within years, stage, histological distributions, and mortality rates. Data were collected from active cancer registry centers, which increased from 23% in 2009 to 47.5% coverage of the whole population by 2012, and mortality data (2010-2015) were obtained from the Turkish Statistical Institute. RESULTS: A total of 16,023 gynecological cancers were evaluated among 116,940 female patients with cancer (13.7%). Average incidence for gynecological cancers was 22.7 of 100,000, representing 8437 total new cases annually. Incidence changes within time were not statistically significant, when evaluated for each tumor type. Estimated risk of gynecological cancer development before the age of 80 years was 3.08% (95% confidence interval, 3.07-3.09). The most common gynecological cancers were uterine corpus cancers, which were followed by ovarian and cervical carcinomas. Ovarian and uterine cancer incidences were closer to European levels rather than Asian countries, whereas cervical cancer incidence was extremely low. Gynecological cancers constituted an important fraction of cancer-related mortality in women by comprising approximately 10.35% of cancer-related deaths. Mortality rates due to gynecological cancers did not show a statistically significant increase within years. CONCLUSIONS: This is the first national cancer registry report to be published for gynecological cancers by the Turkish Governmental Department. As a result, Turkish gynecological cancer epidemiological data were consistent with the data obtained from European and developed countries rather than Asian countries, except for cervical cancer incidence, which is extremely low.

Trends of Gynecological Cancers in Turkey: Toward Europe or Asia?

OBJECTIVE: The aim of this study was to evaluate nationwide gynecological cancer trends in Turkey. METHODS: National cancer registry data (2009-2013) of Turkish Ministry of Health were evaluated. Ovarian, cervical, endometrial, vulvar, vaginal, and tubal cancers are evaluated with respect to age of diagnosis, incidence rates within years, stage, histological distributions, and mortality rates. Data were collected from active cancer registry centers, which increased from 23% in 2009 to 47.5% coverage of the whole population by 2012, and mortality data (2010-2015) were obtained from the Turkish Statistical Institute. RESULTS: A total of 16,023 gynecological cancers were evaluated among 116,940 female patients with cancer (13.7%). Average incidence for gynecological cancers was 22.7 of 100,000, representing 8437 total new cases annually. Incidence changes within time were not statistically significant, when evaluated for each tumor type. Estimated risk of gynecological cancer development before the age of 80 years was 3.08% (95% confidence interval, 3.07-3.09). The most common gynecological cancers were uterine corpus cancers, which were followed by ovarian and cervical carcinomas. Ovarian and uterine cancer incidences were closer to European levels rather than Asian countries, whereas cervical cancer incidence was extremely low. Gynecological cancers constituted an important fraction of cancer-related mortality in women by comprising approximately 10.35% of cancer-related deaths. Mortality rates due to gynecological cancers did not show a statistically significant increase within years. CONCLUSIONS: This is the first national cancer registry report to be published for gynecological cancers by the Turkish Governmental Department. As a result, Turkish gynecological cancer epidemiological data were consistent with the data obtained from European and developed countries rather than Asian countries, except for cervical cancer incidence, which is extremely low.

Trends of Gynecological Cancers in Turkey: Toward Europe or Asia?

OBJECTIVE: The aim of this study was to evaluate nationwide gynecological cancer trends in Turkey. METHODS: National cancer registry data (2009-2013) of Turkish Ministry of Health were evaluated. Ovarian, cervical, endometrial, vulvar, vaginal, and tubal cancers are evaluated with respect to age of diagnosis, incidence rates within years, stage, histological distributions, and mortality rates. Data were collected from active cancer registry centers, which increased from 23% in 2009 to 47.5% coverage of the whole population by 2012, and mortality data (2010-2015) were obtained from the Turkish Statistical Institute. RESULTS: A total of 16,023 gynecological cancers were evaluated among 116,940 female patients with cancer (13.7%). Average incidence for gynecological cancers was 22.7 of 100,000, representing 8437 total new cases annually. Incidence changes within time were not statistically significant, when evaluated for each tumor type. Estimated risk of gynecological cancer development before the age of 80 years was 3.08% (95% confidence interval, 3.07-3.09). The most common gynecological cancers were uterine corpus cancers, which were followed by ovarian and cervical carcinomas. Ovarian and uterine cancer incidences were closer to European levels rather than Asian countries, whereas cervical cancer incidence was extremely low. Gynecological cancers constituted an important fraction of cancer-related mortality in women by comprising approximately 10.35% of cancer-related deaths. Mortality rates due to gynecological cancers did not show a statistically significant increase within years. CONCLUSIONS: This is the first national cancer registry report to be published for gynecological cancers by the Turkish Governmental Department. As a result, Turkish gynecological cancer epidemiological data were consistent with the data obtained from European and developed countries rather than Asian countries, except for cervical cancer incidence, which is extremely low.