Do HPV 16 positive/ASC-H cervical cancer screening results predict CIN 2+ better than other high-risk HPV subtypes?

Objective: To determine whether patients with atypical squamous cells, cannot exclude high grade squamous intraepithelial neoplasia (ASC-H) cytology have a correlation between high-risk human papillomavirus (HPV) type and CIN 2+1 lesion in final pathology. Material and Methods: The study was conducted retrospectively, using data from three tertiary gynecologic oncology centers located in various regions of Turkey. Data from 5,271 patients who had colposcopy between January 2003 and January 2021 were analyzed. Results: A total of 163 patients who had ASC-H cervical cytology test results, based on the Bethesda 2014 classification were eligible, and of these 83 (50.9%) who tested positive for HPV were included in the study. There was no correlation between the occurrence of CIN 2+ lesions and age (p=0.053). If there was any HPV 16 positivity (only HPV 16, HPV 16 and 18, HPV 16 and others) the presence of CIN 2+ lesions in the final pathology increased significantly. In HPV 16 positive ASC-H patients, the probability of CIN 2+ lesions in the final pathology were 72.5% while this rate was 48.1% in HPV 16 negative group (p=0.033). Conclusion: The guidelines do not provide a comprehensive definition of the role of the HPV test in managing ASC-H. Positive high-risk HPV types, especially HPV 16, together with an ASC-H smear result should bring to mind the possibility of high-grade dysplasia.

Clinical features of gestational choriocarcinoma: A retrospective bicentric study.

OBJECTIVE: To investigate the clinicopathological features, prognostic factors, treatment, clinical response, and outcome of gestational choriocarcinoma (GCC). MATERIALS AND METHODS: A retrospective review was made of the clinicopathological and survival data of 13 patients who were diagnosed and treated for GCC in two referral centers in Turkey between 1992 and 2020. RESULTS: The median age of patients was 36 years (range, 27-54 years), and seven were ≤39 years. The antecedent pregnancy was a term in nine (69.2%) cases, and the risk score was ≥7 in 11 (84.6%). According to the International Federation of Gynecology and Obstetrics 2009 staging, eight cases were in stage I, two in stage III, and three in stage IV. With the exception of one patient, all the others received combination chemotherapy (CT), and two of those were also treated with radiotherapy. Chemoresistance developed in 50% (6/12), and second-line CT was given to four of these. The overall complete response rate was 69.2%. Four patients died of chemoresistance and disease progression, all of them were with antecedent-term pregnancy, had high scores ≥7, and had metastases. CONCLUSION: GCC is a unique subtype of gestational trophoblastic neoplasia, which differs from others in terms of poor prognosis, a frequent tendency to early metastasis, and resistance to treatment. To be able to achieve the most efficient therapy and prognosis, histopathology-based risk models should be developed.

Does the addition of metformin to carboplatin treatment decreases ovarian reserve damage associated with carboplatin usage?

BACKGROUND: We aimed to determine whether adding metformin to carboplatin treatment would reduce the damage to ovarian reserve associated with carboplatin use. METHODS: We included 35 adult female non-pregnant albino Wistar rats approximately three months old, weighing 220-310 g. The rats were divided into five groups of seven rats according to the treatment they received. Carboplatin and salin was given to Group 2, and carboplatin plus metformin was given to Group 3. Group 4 was administered only metformin. Group 5 was administered only salin. Carboplatin was given to Groups 2 and 3 as a single dose on the 15th day, while metformin was given to Groups 3 and 4 during the 28-day experiment. After oophorectomy, histopathologic analyses of primordial, primary, secondary, and tertiary Graff follicles according to the epithelial cells surrounding the oocyte and total follicular number were conducted per section. Serum Anti-Mullerian Hormone (AMH), tissue catalase, and malonyl dialdehyde levels were measured and compared within each group. RESULTS: The baseline and 15th-day serum AMH values of the menstrual cycle were compared among the groups, and no statistically significant differences were observed (p > 0.05). Group 3, which was given both carboplatin and metformin, had statistically significantly higher 28th-day AMH levels than Group 2, which was given only carboplatin and saline (p < 0.001). The number of primordial follicles in Group 3 was found to be statistically significantly higher than in Group 2 (p < 0.001). Tissue catalase enzyme levels in Group 3 were statistically significantly higher than in Group 2 (p < 0.001). Tissue malondialdehyde levels in Group 2 were statistically significantly higher than tissue malondialdehyde levels in Groups 3 and 4 (p < 0.001). CONCLUSIONS: Metformin may attenuate carboplatin-induced ovarian damage, possibly through its antioxidative effects.

Clinicopathological features of atypical glandular cells, not otherwise specified, on cervicovaginal pap smears.

OBJECTIVE: The Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC-NOS). METHODS: We retrospectively reviewed Pap smear tests that resulted as AGC-NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC-NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed. RESULTS: Two hundred fifty-four patients with AGC-NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively. CONCLUSIONS: Patients diagnosed with AGC-NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC-NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics.

Post-recurrence survival analysis of patients with pulmonary recurrence from gynaecologic cancers: a multi-institutional analysis of 122 patients.

In this retrospective study, patients with epithelial gynaecologic cancer with pulmonary recurrence (PR) were evaluated from five national gynaecologic oncology clinics. Patients with a diagnosis of primary endometrial, ovarian/fallopian tube/peritoneal, cervical or vaginal/vulvar tumours who developed an initial PR were included in the study A total of 122 patients were included in the study. The median follow-up time after recurrence was 7.5 (range, 1-84) months. The 2-year PRS was 48% in the main cohort. The risk of death was more than seven times higher in patients who did not receive salvage chemotherapy compared with those who did (hazard ratio: 7.6, 95% CI: 3.0-18.9; p < .001). When squamous cell carcinoma was compared with the other tumour types, the risk of death increased more than three times (hazard ratio: 3.7, 95% CI: 1.4-9.6; p = .007).IMPACT STATEMENTWhat is already known on this subject? Pulmonary recurrence (PR) from gynaecologic malignancies is rare and can cause major clinical problem. Therefore, defining the clinical and pathologic characteristics and recurrence patterns are essential.What the results of this study add? This study demonstrates non-squamous subtype and salvage chemotherapy at PR were associated with improved survival.What of these findings for clinical practice and/or further research? To the best of our knowledge, our study is the largest study to investigate the clinico-pathologic characteristics, recurrence patterns, treatment options, and post-recurrence survival (PRS) in patients with PR from epithelial gynaecologic cancers. Future research should examine the underlying causes of these findings.

Prognostic value of systemic inflammatory response markers in cervical cancer.

We investigated the association between preoperative ratios of inflammatory markers and the prognosis in patients with invasive cervical cancer (CC). In this single-centre study, we retrospectively enrolled 163 CC patients who underwent radical hysterectomy between February 2008 and October 2018. Among the evaluated ratios, a high neutrophil-to-lymphocyte ratio (N/L) was significantly associated with deep stromal invasion and tumour size larger than 2 cm, whereas a high M/L was significantly related to advanced-stage CC (IB3-IIIC2), lymphatic metastasis (total) and pelvic lymph node metastasis (p= .002, p= .046 and p= .046, respectively). The neutrophil count plus monocyte-to-lymphocyte ratio (NM/L) and platelet-to-lymphocyte ratio (P/L) were significantly higher in patients with deep stromal invasion, advanced stage and tumour size larger than 2 cm (p=.01, p=.044 and p=.007; p=.004, p=.005 and p=.003, respectively). In the multivariate analysis, high NM/L (>168) was associated with a statistically significant hazard ratio of 3.04 (95% CI: (1.38-6.72); p=.006) for recurrence and 9.05 (95% CI: (2.10-38.99); p=.003) for death. Both stage and NM/L are independent prognostic factors that are significantly associated with recurrence and overall survival in CC.Impact StatementWhat is already known on this subject? Previous studies suggested that there is a relationship between inflammation and the formation, development and progression of cancer. However, the relationship between cervical cancer (CC) and inflammatory blood parameters is incompletely understood.What do the results of this study add? This study investigated the relationship between systemic blood inflammatory ratios and clinicopathological patient characteristics and disease outcomes in CC.What are the implications of these findings for clinical practice and/or further research? According to this study, systemic blood inflammatory ratios may help predict the prognosis and survival of patients with CC.

Malignant struma ovarii: From case to analysis.

AIM: To evaluate the clinico-pathologic features, treatment options, prognostic factors, and survival outcomes of malignant struma ovarii based on a systematic literature review in association with our case study. METHODS: A systematic review of the medical literature was performed to identify articles about malignant struma ovarii from January 1983 until July 2020. We evaluated 178 cases. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) of the entire cohort was 72.5% and 91%, respectively. In univariate analysis, younger age (<43 years), whole strumal cyst diameter >95 mm, presence of a histologic type other than papillary classic-type thyroid carcinoma within the tumor and lymphovascular space invasion were related to poor PFS. Patients who received radioactive iodine ablation (RIA) before the treatment failure had significantly higher PFS than those who did not receive RIA (94.9% vs. 64.8%, p = 0.041, respectively). In univariate analysis, PFS was significantly higher in patients who underwent gynecologic surgery followed by thyroidectomy and RIA compared with those who had surgical treatment only (94.5% vs. 64.3%, p = 0.05, respectively). However, this result could not be identified as an independent prognostic factor in multivariate analysis (p = 0.207). Younger age and absence of capsular involvement were related to significantly increased OS. Histologic type was the only independent prognostic factor for PFS (hazard ratio: 3.30, 95% confidence interval: 1.122-9.748; p = 0.030) CONCLUSION: The most common histologic subtype was the papillary classic type. The presence of a histologic type other than the classic papillary thyroid carcinoma within the tumor was an independent adverse prognostic factor.

The role of lymphadenectomy in patients with stage III&IV uterine serous carcinoma: Results of multicentric Turkish study.

OBJECTIVE: The aim of this study was to evaluate clinicopathological features, oncological outcome and prognostic factors for recurrence in advanced stage uterine serous carcinoma (USC) patients. METHODS: Patients with 2009 International Federation of Gynecology and Obstetrics stage III&IV uterine serous carcinoma were enrolled from 4 gynecologic oncology centers and a study group was created. Response to therapy was evaluated according to the WHO criteria. Progression-free survival (PFS) and overall survival (OS) estimates were determinated by using the Kaplan-Meier method. Survival curves were compared with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Entire cohort included 63 patients. Median age of cohort was 64 years. Thirty-five (55.6 %) patients were stage IV. Lymphadenectomy was performed in 57 (90.5 %) patients and lymph node metastasis was positive in 45 (71.4 %) patients. Maximal cytoreduction (no residue tumor) was achieved in 53 (84.1 %) patients. However, optimal cytoreduction (residue tumor ≤1 cm) was achieved in 6 (9.5 %) patients and suboptimal cytoreduction (residue tumor >1 cm) was achieved in 3 (4.8 %) patients. Median follow-up time was 19 (range;1-152) months. Complete clinical response was obtained in 58 (92.1 %) patients after standard adjuvant therapy. Disease failure was detected in 25 patients. Study group had a 2-year PFS of 51 % and 2-year OS of 80 %. On multivariate analysis, performing lymphadenectomy was an independent prognostic factor for PFS (Odds ratio: 24.794, 95 % Confidence Interval: 4.214-145.869; p < 0.001). CONCLUSION: Lymphadenectomy should be a part of the standard surgical therapy in advanced stage USC.

Retrospective Analysis of Pure Ovarian Immature Teratoma in Patients Aged 15-39 Years: A Turkish Multicenter Study.

Purpose: To evaluate the clinicopathological characteristics and surgical outcomes in patients with pure ovarian immature teratomas (POITs). Materials and Methods: In this multicenter study, a retrospective review was made of the databases of six Gynecology Oncology Departments in Turkey to identify patients with POITs who had undergone surgery between 1993 and 2019. Results: Evaluation was made of 48 patients with a median age at diagnosis of 22.5 years (range, 15-37 years). In 40 (83%) patients, stage I was determined and in eight patients, an advanced stage (IIIB, IIIC, and IVB) was determined. Tumors were found to be grade I in 17 (35.4%) cases, grade II in 12 (25%), and grade III in 19 (39.6%). Fertility-sparing surgery was applied to 42 (87.5%) patients and radical surgery to 6 (12.5%). The median follow-up was 60 months (range, 3-246 months). Recurrence was seen in seven patients, all with grade III tumors. In the final pathological examination of recurrent tumors, mature teratoma was reported in five patients, and immature teratoma in one patient. Salvage surgery was not performed in one patient as the tumor was unresectable and so a regimen of bleomycin, etoposide, and cisplatin (BEP) was administered. Conclusion: POITs are rare tumors seen at a young age, and benign or malignant relapse can be seen in these tumors. In this cohort, the malignant recurrence rate was 4.1%, and the benign recurrence rate was 10.4%. All the recurrences were in grade III tumors. Benign recurrences can be treated with surgery alone and the malignant group should be treated with surgery followed by chemotherapy.

Assessment of serum angiotensin-converting enzyme in patients with epithelial ovarian cancer.

BACKGROUND AND AIMS: Clinicopathologic and molecular studies have provided new insights and understanding on the pathological events during ovarian carcinogenesis. Moreover, angiotensin II-enhanced tumor cell invasion via type 1 angiotensin II receptor in ovarian cancer cell lines was recently demonstrated. It has been suggested that renin-angiotensin system (RAS) activity increases in diseases involving the female reproductive system. In the present study, we aimed to analyze the possible relationship between the levels of circulating angiotensin-converting enzyme (ACE), an important molecule of RAS, and ovarian cancer (OC). MATERIALS AND METHODS: This study was conducted in 41 epithelial OC patients (mean age 56.1 ± 10.2 years) and 19 healthy controls (mean age 53.4 ± 13.1 years). Clinical and laboratory features are summarized. Serum ACE and Ca-125 levels were measured using commercially available laboratory kits. RESULTS: Serum ACE levels of epithelial OC patients and controls were 30.58 ± 13.37 and 14.15 ± 3.67, respectively. Serum ACE levels were significantly elevated in epithelial OC patients in comparison to healthy controls. Ca-125 levels of epithelial OC patients were also significantly elevated in epithelial OC patients. No correlation was observed between ACE levels and Ca-125 levels. In epithelial OC patients, serum ACE levels did not differ according to stages and pathologic subtypes of the patients. CONCLUSION: Our results showed that serum ACE levels were increased in OC patients. Being an important component of RAS, circulating ACE might be associated with ongoing pathobiologic events in ovarian carcinogenesis. Therefore, targeting the RAS pathway could provide a future treatment strategy for this cancer type.

Sperm-associated antigen 9 is a promising marker for early diagnosis of endometrial cancer.

BACKGROUND: Sperm-associated antigen 9 (SPAG9) has been recently proposed as a novel biomarker for early diagnosis of several human tumors, including ovarian, cervical and breast cancers. Its clinical value remains to be clarified for endometrial cancer (EC). In this study, we investigated the utility of serum SPAG9 levels in diagnosis of EC and its association with important clinicopathological parameters. MATERIALS AND METHODS: This cross-sectional study was performed at a tertiary women's referral center in Ankara, Turkey. Preoperative serum samples were collected from patients surgically treated for endometrial cancer between June 2012-April 2013. Similar aged women with a biopsy proven benign endometrium were used as controls. Serum SPAG9 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method and assessed for links with clinicopathological factors. Receiver operating characteristic (ROC) curve analysis was performed to assess power of SPAG9 levels for EC prediction. P values less than 0.05 were considered statistically significant. RESULTS: A total of 63 women with EC and 27 with benign endometrium were included in the study. Mean age in the EC group was 58.7±1.1. Median SPAG9 levels in the EC and control groups were 18.3 (range, 12.7-53.8) and 14.1 (range, 4.3-65.3), respectively (p<0.001). A cut-off value of 17 ng/ml for SPAG9 predicted presence of malignant endometrium with 74% sensitivity and 83% specificity [Area under curve (AUC)=0.82, p<0.001]. SPAG9 levels did not demonstrate any significant association with histological type, FIGO stage, tumor grade, size, myometrial invasion, lymphovascular space invasion, cervical involvement, adnexal involvement, peritoneal cytology or lymph node status (all p>0.05). CONCLUSIONS: Testing for SPAG9 may be useful for early detection of EC in asymptomatic high-risk women. Its role in post-treatment follow-up and early detection of recurrence should be assessed in future trials.