Comparison of programmed death-ligand 1 expression in adenocarcinoma and squamous cell carcinoma of the cervix in paraffin blocks of patients with cervical cancer.

AIMS: Cervical cancer (CC) is a common malignancy in women, predominantly caused by human papillomavirus. The most subtypes are adenocarcinomas (AC) and squamous cell carcinomas (SCC), which show various features and treatment responses. Programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) as Immune checkpoint molecules, play a role in immune evasion. We investigated PD-L1 expression in AC and SCC of the cervix and explored its link to clinical characteristics. METHODS AND RESULTS: The present cross-sectional research was done between 2016 and 2022 on samples in Shahid Beheshti University of Medical Sciences-affiliated hospitals in Iran. Histological tissue samples of CCs (16 AC and 48 SCC) were assessed, and clinical information was obtained by reviewing their medical documents. PD-L1 expression was evaluated by immunohistochemistry and we used the combined positive score. SCC cases showed a higher (not significant) PD-L1 expression. The PD-L1 expression and clinical characteristics were not significantly correlated in both subgroups. CONCLUSION: Although SCC cases exhibited higher PD-L1 expression, this difference was non-significant. More investigations should highlight the role of PD-L1 in CC and the potential benefits of immunotherapy.

The Effect of Radiofrequency Therapy on Sexual Function in Female Cancer Survivors (Gynecologic and Breast) and Non-cancer Menopausal Women: A Single-Arm Trial.

Introduction: Up to 90% of postmenopausal women and female cancer survivors may be affected by the genitourinary syndrome of menopause (GSM), with a negative impact on sexual function and quality of life. A novel energy-based device among the treatment options for GSM is radiofrequency therapy (RFT). RFT is a treatment option that uses energy from radio waves to heat the tissue. The objective of this study was to assess the impact of RFT on sexual function in female cancer survivors (gynecologic and breast) and non-cancer menopausal women. Methods: In a single-arm prospective trial, the efficacy of RFT in both female cancer survivors (gynecologic and breast) and non-cancer menopausal women with sexual dysfunction at a tertiary and referral center (Imam Hossein Medical Center, Tehran, Iran) was evaluated between April 2022 and December 2022. The study protocol consisted of 3 monthly RFT sessions. Examination was performed at baseline (T0) and 3 months after the last RFT session (T1). The primary outcome was sexual function, which was assessed using the Female Sexual Function Index (FSFI). In addition, adverse events were evaluated during treatment and at T1. Results: A total of 37 female cancer survivors (mean [SD] age: 49.4 [8.9] years) and 37 non-cancer menopausal women (mean [SD] age: 53.8 [5.5] years) were enrolled. Patients exposed to RFT showed a significant improvement in FSFI scores when compared to baseline scores for both female cancer survivors (13.07, 95% CI: 12.27 - 13.86) and non-cancer menopausal women (13.18, 95% CI: 12.34 - 14.03). There was no difference in FSFI total score improvement between the two groups (t(72)=0.06, P=0.951). There were no serious adverse events associated with RFT. Conclusion: The efficacy of RFT as a treatment for sexual dysfunction has been demonstrated in both non-cancer menopausal women and female cancer survivors. In both groups, a significant improvement was confirmed.

Endometrial cancer in women with abnormal uterine bleeding: Data mining classification methods.

Background: Over the last decade, artificial intelligence in medicine has been growing. Since endometrial cancer can be treated with early diagnosis, finding a non-invasive method for screening patients, especially high-risk ones, could have a particular value. Regarding the importance of this issue, we aimed to investigate the risk factors related to endometrial cancer and find a tool to predict it using machine learning. Methods: In this cross-sectional study, 972 patients with abnormal uterine bleeding from January 2016 to January 2021 were studied, and the essential characteristics of each patient, along with the findings of curettage pathology, were analyzed using statistical methods and machine learning algorithms, including artificial neural networks, classification and regression trees, support vector machine, and logistic regression. Results: Out of 972 patients with a mean age of 45.77 ± 10.70 years, 920 patients had benign pathology, and 52 patients had endometrial cancer. In terms of endometrial cancer prediction, the logistic regression model had the best performance (sensitivity of 100% and 98%, specificity of 98.83% and 98.7%, for trained and test data sets respectively,) followed by the classification and regression trees model. Conclusion: Based on the results, artificial intelligence-based algorithms can be applied as a non-invasive screening method for predicting endometrial cancer.

Comparison of Ki67 index and P16 expression in different grades of cervical squamous intraepithelial lesions.

Background: the assessment of P16 expression and Ki-67 proliferative index is now proposed as an adjunct test for the diagnosis of high-risk precursor lesions for cervical cancer. The aim of the present study was to elucidate the quality expression of P16 and quantification Ki-67 index in different types of cervical intraepithelial neoplasia and also to determine the cutoff for Ki67 index to predict the severity of CIN lesions. Methods: This cross-sectional study was conducted on patients with colposcopic indication. Selected samples with different CIN grades were examined for P16 and Ki-67 index by immunohistochemical (IHC) methods. Results: All LSIL (CIN I) cases were negative for P16, while in 58.7% of HSIL cases (CIN 2/3), P16 was positive. The mean Ki67 index in the present study was 3.13 ± 2.65 in the upper two/third of the squamous epithelium in the LSIL group and 19.04 ±36.40 in the HSIL group, which was statistically significant. Also, the mean Ki67 index in full thickness squamous epithelium in HSIL group was significantly higher than LSIL. The sensitivity of P16 and Ki67 index in our study was 58.73%, 66.67% and the specificity was 100% and 100%, respectively. Conclusion: Assessment of P16 expression and Ki67 index can be used to distinguish low grade (CIN1) intraepithelial lesion from high grade (CIN2/3) intraepithelial or precancerous lesions.

Screening of Lynch syndrome in endometrial cancer in Iranian population with mismatch repair protein by immunohistochemistry.

Background: Lynch syndrome (LS) is one of the commonest genetic cancer syndromes, with an incidence rate of 1 per 250-1000 population. The aim of this study was to evaluate the frequency and characteristics of MMR deficiency in endometrial cancer in Iranian women. Methods: One hundred endometrial carcinoma cases who referred to the gynecological oncology clinic of Imam Hossein Medical Center located in Tehran, Iran, from 2018 to 2020 were included in the study. Immunohistochemistry (IHC) evaluation was performed mainly on the hysterectomy specimens of all endometrial cancer (EC) patients to assess MMR proteins (MLH1, MSH2, MSH6, and PMS2) expression. Results: A total of 23 out of 100 (23%) cases were identified through IHC screening to be MMR-deficient. The most common types were loss of MLH1/PMS2 (17.4%) and solitary MSH2 (17.4%) expressions followed by PMS2/MSH2 loss (13%). MMR deficiency (dMMR) histopathology was significantly overrepresented in patients with family history of cancer or Lynch syndrome (LS) associated cancers (p-values of 0.016 and 0.005, respectively). The rate of myometrial invasion and lower uterine segment involvement were also significantly higher in dMMR EC patients compared to MMR-intact EC (p-value of 0.021 and 0.018, respectively). Conclusion: MMR deficiency, observed in 23% of endometrial cancer cases, was associated with higher rates of poor prognostic factors including myometrial invasion and lower uterine segment involvement. The presence of positive family history of cancer and family history of LS-associated cancer increased the probability of MMR-deficiency in endometrioid endometrial cancer to 47% and 70%, respectively.

Prevalence and Genotype Distribution of Human Papillomavirus Infection among 12 076 Iranian Women.

INTRODUCTION: Human papillomavirus (HPV) infection is one of the major health concerns of women in developing countries. This study gives an insight into the prevalence and genotype distribution of HPV infection and compares it with Pap smear results among Iranian women. METHODS: In this study, 12 076 Iranian women underwent routine examination from November 2016 to November 2018 using HPV Direct Flow CHIP System for HPV DNA typing. Cytology was undertaken for 5138 samples. RESULTS: Overall HPV prevalence was calculated at 38.68%. The most frequent HPV types were HPV 6, 16, 11, 62/81, 52 and 54. The most high-risk HPV (HR-HPV) types were HPV 16, 52, 18, 39, 31 and 51. These 2 groups represent approximately half of all HPV types detected, 47% and 55%, respectively. Among individuals who underwent cytological tests, 135 individuals (2.63%) were cytologically positive. In this group, 81 individuals (60%) were HPV positive, 62 (76%) of whom were HR-HPV positive, most frequently with HPV 16 (34%). CONCLUSION: This study highlights the urgent need for public education and early diagnosis using HPV screening tests to prevent cervical cancer.

Diagnostic Role of Papanicolaou Smear, Hemoglobin, Blood Group, and Other Clinical Symptoms in Detecting Endometrial Carcinoma: A Clinicopathological Study of 175 Iranian Women with Endometrial Carcinoma.

OBJECTIVES: Endometrial carcinoma (EC) is a common gynecologic malignancy in the female genital tract, especially in postmenopausal women. The current study aimed to analyze Papanicolaou (Pap) smear in patients with EC to assess the relationship between EC and abnormal cells in Pap smear, ABO blood group, and hemoglobin anemia. MATERIALS AND METHODS: A retrospective study was conducted on 175 patients with EC in Imam Hossein Hospital, Tehran, Iran, during the period from 2013 to 2019. The histology information of cases was extracted from the hospital database, and Pap smear slides were taken from pathological archives. The acquired information and slides were then reviewed by an expert pathologist in the hospital. The data were analyzed in SPSS (version 18) by the Chi-square test, Fisher's exact test, and independent-samples t-test. P < 0.05 was assigned as significant. RESULTS: The mean age of patients was 54.47 ± 11.34, ranging from 32 to 85 years, and 31.4% of the patients were premenopausal women. Grade III, invasion ≥ 50% of myometrial, and advanced stage (III and IV) were diagnosed in 30%, 7.4%, and 22.86% of the patients, respectively. The most common histological types of EC were endometrioid (66.9%), papillary (10.3%), and malignant mixed Mullerian tumor (5.7%). The abnormal Pap smear was achieved only in 37 EC patients (21.1%). Endometrial cells, atypical squamous cells of undetermined significance, and atypical glandular cells were observed in 56.8%, 29.7%, and 13.5% of the patients > 40 years of age with abnormal Pap smears, respectively. In patients with normal Pap smears, the most common results were inflammation in 75.1% and atrophy in 14.6% of the patients. Abnormal uterine bleeding was the most important problem observed in patients with EC. CONCLUSION: The efficacy of Pap smear in detecting EC is limited. Therefore, women with EC, >40 years of age, with heavy bleeding, anemia, O blood group, inflammation, and atrophy in Pap smear in the past 3 years need to be precisely checked up for EC. These items can be added as new criteria for EC screening procedures.

Evaluation of Neutrophil-Lymphocyte Ratio as a Prognostic Factor in Cervical Intraepithelial Neoplasia Recurrence.

Background: Immune system status is a factor related to cervical intraepithelial neoplasia (CIN) recurrence. neutrophil-lymphocyte ratio (NLR) is a useful factor in assessing the immune status. The aim of this study was to evaluate the prognostic value of NLR factor for CIN recurrence in patient who underwent excisional procedure and its relationship with recurrence free survival (RFS). Methods: In this historical cohort study, a population of 307 patients with CIN (confirmed by excisional pathology) from 2009 to 2017 were selected. NLR and hematologic factors were measured before surgery and the follow-up records of these patient were analyzed. The recurrence rate and RFS were assessed during the follow-up phase. Results: The NLR cut-off point of 1.9 was determined using the Youden Index. NLR<1.9 (low NLR) and NLR≥1.9 (high NLR) were observed among 68.1% and 39.1% of patients, respectively. Univariate analysis showed that higher NLR values (P<0.001), absolute neutrophilic counts (ANC) (P<0.001) and platelet lymphocytic ratios (PLR) (P=0.002) were significantly associated with reduction in RFS. The results of Cox regression showed that removing more tissue during excision (HR = 0.325; 95% CI (0.936-0.136) significantly reduced the hazard of recurrence, higher NLR (HR = 4.55; 95% CI) (1.97-10.51) and white blood cell (WBC) count levels (HR =1.27; 95% CI, 1.04-1.55), significantly decreased RFS, but PLR and ANC associated with RFS were not confirmed by Cox regression. Conclusion: NLR and total WBC count might be prognostic factors involved in the prediction of recurrence and RFS in CIN patient underwent excisional procedure. To confirm these results, more prospective studies with larger sample sizes are needed.

Model for Prediction of Optimal Debulking of Epithelial Ovarian Cancer

Background: Primary cytoreduction surgery followed by chemotherapy is the cornerstone treatment for epithelial ovarian cancer (EOC). In patients with a low probability of optimal primary surgical debulking, neoadjuvant chemotherapy (NACT) followed by interval debulking increases the chance of optimal surgery. The aim of this study was to develop a model to identify preoperative predictors for suboptimal cytoreduction. Methods: Medical records of patients with EOC who underwent primary cytoreductive surgery in a referral tertiary gyneco-oncology center were reviewed from 2007 to 2017. Data were collected on a range of characteristics including demographic features, comorbidities, serum tumor markers, hematologic markers, preoperative imaging, surgical procedures, and pathologic reports. Univariate and multivariate analyses were performed to clarify the ability of preoperative factors to predict suboptimal primary surgery. Results: The majority of patients (71.3%) who underwent primary cytoreductive surgery were optimally debulked. Based on the Youden index, the best cut-off point for the serum CA125 level to distinguish suboptimal debulking was 420U/ml with 0.730 (95%CI:0.559 to 0.862) sensitivity and 0.783 (0.684 to 0.862) specificity. Multiple logistic regression results showed that serum CA125 level >420 U/ ml (p value <0.001), the presence of liver metastasis on preoperative imaging (p value: 0.041) and ascites (p value: 0.032) or massive ascites (p value:0.010) significantly increased the risk of suboptimal debulking (logit p = 2.36 CA125 level +1.85 Liverinvolvement +1.68 presence of Ascites+ 2.28 Massive Ascites). Conclusion:The present study suggests that a serum CA125 level >420 U/ml, the presence of ascites or massive ascites and liver metastasis are strong predictors of suboptimal primary surgery in cases of EOC. Based on the constructed model, with any of these 4 factors, the probability of suboptimal debulking in EOC is more than 80%.

Comparison between performance of single-fiber reflectance spectroscopy (SFRS) system and colposcopy: a phase III trial.

Herein, the performance of single-fiber reflectance spectroscopy (SFRS) in detection of cervical pre-cancerous squamous intraepithelial lesions (SIL) was compared with colposcopy. Based on the previous results obtained from 167 samples and finding the contributing parameters in differentiating SILs from non-SILs, a user-friendly interface was developed to detect the SILs using SFRS system. Detection of SILs in 301 patients was performed by both SFRS system and routine colposcopy. In addition to physician-determined sites, four quarters of the cervix were measured by SFRS system and suspicious lesions detected by either method were biopsied. Histopathologic results of the biopsied species were compared to the physician judgments based on colposcopy and the results of SFRS system. SFRS could differentiate between SILs and non-SILs with mean sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 38.3, 60.9, 15.2, and 84.3%, respectively. These values were obtained as 88.3, 10.6, 15.4, and 83.1% for the colposcopy, respectively. Although sensitivity of SFRS in detection of SILs is about twofold less than the colposcopy, it can reduce the number of unnecessary biopsies by a factor of more than 5.5. Therefore, the aid of SFRS system to the physician can reduce the number of unnecessary biopsies. On the other hand, both colposcopy and SFRS methods equally suffer from low detection worth in terms of positive/negative predictive values. In conclusion, using the online, simple and non-invasive SFRS system to choose between several suspicious sites in a patient in the clinic may be recommended.

Value of Sentinel Lymph Node (SLN) Mapping and Biopsy using Combined Intracervical Radiotracers and Blue Dye Injections for Endometrial Cancer

Background: Lymphadenectomy, as part of the initial surgical staging of patients with endometrial carcinoma, remains a controversial topic in gynecologic oncology. Sentinel lymph node (SLN) mapping has become a well-accepted procedure for melanomas and breast cancer; a number of investigators have begun to explore the utility and accuracy of this technique with regard to endometrial cancer. Aim: This study was conducted to evaluate SLN mapping of early stage endometrial cancer with blue dye in conjunction with a radioactive tracer. Subjects and methods: In this prospective cross-sectional study, patients with stage I and II endometrial cancer who were candidates for systemic lymph node dissection during surgery were enrolled, some underwent lymph node mapping and SLN biopsy using combined intra cervical radiotracer and blue dye injections and some applying only an intra cervical radiotracer. SLNs and other lymph nodes were sent for pathological assessment. Sensitivity, specificity, the positive predictive value, and the negative predictive value were calculated as predictive values for the radiotracer and blue dye. Results: Pre-operative lymph node mapping showed SLN in 29 out of 30 patients. Intra operations in 29/30 patients, SLNs were harvested by gamma probe; in 13 out of 19 patients SLNs were detected by blue dye. The median number of SLNs per patient was 3 and the total number of SLNs detected was 81. Four patients had positive pelvic lymph nodes. All of the positive nodes were SLNs. Using this technique (radiotracer and blue dye) an overall detection rate of 96.7%, an NPV of 100%, a sensitivity of 100% and a specificity of 3.85% were achieved. Conclusion: Results of SLN research for endometrial cancer are promising and make feasible the possibility of avoiding unnecessary aggressive surgical procedures in near future by advances in SLN mapping.

Rhabdomyosarcoma of Cervix: A Case Report.

INTRODUCTION: Rhabdomyosarcoma has known as a highly malignant soft tissue sarcoma. It has been the most common soft tissue sarcoma in childhood, accounting for about 3 to 4 % of all cases of childhood cancer. Rhabdomyosarcoma was rare in adults, accounting for 3% of all soft-tissue sarcomas. embryonal rhabdomyosarcoma of female genital tract including uterine cervix in an adult was rare. CASE PRESENTATION: This study has reported a 33-year-old woman presented with abnormal vaginal discharge. Gynecologic examination revealed a cervical mass with grape- like feature protruding into vagina with posterior- superior vaginal wall involvement. Biopsy has performed and pathologic examination was consistent with embryonal botryoid type rhabdomyosarcoma. She has undergone the staging work up measurements including thoracic computed tomography (CT) scan, abdominopelvic magnetic resonance imaging (MRI), bone scan and bone marrow examination. In exception of abdominopelvic MRI, with 2 suspicious pelvic lymph nodes in addition of cervical mass, all others were normal. Radical hysterectomy with lymph node debulking and ovarian preservation has performed. Final results have shown embryonal botryoid type rhabdomyosarcoma of cervix. ovaries, endometrium, parametrium, and follopian tubes were unremarkable. Pelvic lymph nodes pathology and intraabdominal fluid cytology were negative for malignancy. Lymphovascular invasion was identified. She has advised for adjuvant chemotherapy. CONCLUSIONS: This case has reminded that embryonal rhabdomyosarcoma could occur in uncommon site and older female. Longer follow up of these cases has required due to lack of survival data for embryonal rhabdomyosarcoma of this site and age group.

Investigating Preoperative Hematologic Markers for Prediction of Ovarian Cancer Surgical Outcome.

PURPOSE: The current study aimed at assessing the association between neutrophil-lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) for the prognosis of the surgical outcome of epithelial ovarian cancer (EOC). MATERIALS AND METHODS: EOC patient medical records of surgical operations between January, 2005 and December, 2015 were reviewed and their data of clinicopathological complete blood counts (CBCs) and surgical outcomes were collected. To assess their effects on surgical outcomes, PLR and NLR optimal predictive values were determined and then compared with each other. RESULTS: A statistically significant relation was found between surgical outcomes and NLR and PLR (p<0.001 and p<0.001), for which new cutoff points were gained (PLR: 192,3,293; NLR: 3). The sensitivity and specificity were 0.74 and 0.67, respectively for PLR and 0.74 and 0.58, for NLR. CONCLUSIONS: NLR and PLR seem to be useful methods for the prediction of surgical outcomes in patients with EOCs. Increased NLR and PLR proved to be beneficial for poor surgical outcomes. Moreover, PLR increase showed further help in the predicting outcome of EOC suboptimal debulking.

Neuroendocrine carcinoma of the ovotestis: A case report and review of literatures.

BACKGROUND: Neuroendocine carcinoma of the gynecologic tract is rare and poses a significant clinical challenge because of tumor heterogeneity and lack of standardized guidelines for treatment. Ovotestis refers to the histology of a gonad that contains both ovarian follicles and testicular tubular elements. Ovotesticular disorder of sexual development occurs in fewer than 10% of all disorders of sexual development. Gonadal tumors with malignant potential occur in 2.6% of all cases of ovotesticular disorder of sexual development. CASE: Here we represent a 77-year-old woman with primary amenorrhea, infertility and 10cm solid mass in left adnex with 46 XY in karyotype with ovotestis neuroendocrine neoplasm in pathology report which was treated with a multi-modality manner including surgery and chemotherapy but she came back with pulmonary metastasis after 2 cycles of chemotherapy. For women who present with a stage 1 primary ovarian neuroendocrine tumor the prognosis is excellent with greater than 90% survival. Neuroendocrine tumor of the ovary represents 3 % of all neuroendocrine tumors. The prevalence of ovotestis is 1/20000 births. For women with more advanced disease, the prognosis is poor. Neuroendocrine carcinoma of the ovary is a rare and aggressive tumor commonly associated with other surface epithelial and germ cell neoplasms. The prevalence of ovotestis is 1/20000 births and gonadal malignancies are the most reported neoplasm affected the ovotestis. Here we report a case of ovotestis which is presented with neuroendocrine carcinoma and poor prognosis. CONCLUSION: Neuroendocrine carcinoma of the ovary is a rare and aggressive tumor commonly associated with other surface epithelial and germ cell neoplasms. The prevalence of ovotestis is rare and gonadal malignancies are the most reported neoplasm affected the ovotestis.

Thirteen -weeks ovarian pregnancy following in vitro fertilization for primary infertility treatment: A case report.

BACKGROUND: Ovarian pregnancy constitutes 0.15-3% of all ectopic pregnancies. The incidence of ectopic pregnancy is on the rise owing to evolution in assisted reproductive techniques (ART). The incidence reported following In vitro fertilization (IVF) or embryo transfer (ET) is 0.27% per clinical pregnancy. CASE: We present a case of a 13-weeks ovarian pregnancy following IVF-ET and through a review of the literature, the specific symptomatology, diagnostic criteria, and treatment of this particular pathology will be described. CONCLUSION: Ovarian pregnancy is a rare condition and its diagnosis is difficult and relies on criteria based on intraoperative and histopathological findings. The management is, in spite of medical improvement, based on surgery. But the trend has shifted towards conservative surgeries in majority of cases.