Archives of Iranian Medicine

Clinicopathological Pattern of Endometrial Specimens in Women with Abnormal Uterine Bleeding and Ultrasonography Correlation

Background: Abnormal uterine bleeding (AUB) refers to any symptomatic deviation from normal menstruation. AUB is a common gynecological disorder in non-pregnant women of reproductive age, accounting for approximately 33% of gynecological outpatient visits. The early diagnosis and management cause of AUB is important because of increased incidence of endometrial carcinoma with rapid growth. Transvaginal ultrasound is non-invasive imaging technique used to find endometrial carcinoma before referring patients for invasive techniques. Dilatation and curettage (D&C) and endometrial biopsy are surgical procedures that scrape the endometrial lining of the uterus for diagnosis and treatment. The aim of this study is to describe the clinicopathologic pattern of endometrial specimens in women with AUB and ultrasonographic correlation. Methods: Tissues from endometrial biopsy and curettage of 411 patients with AUB who referred to Shahid Mohammadi hospital were prospectively selected from 2021 to 2023. Patients were divided into three groups based on age and menstrual status including: premenopausal (18-39 years), perimenopausal (40-49 years) and postmenopausal (≥50 years). The results were correlated to patient’s age and other data and evaluated with statistical analysis. Results: During the two-year study period, a total of 411 endometrial specimens with clinical diagnosis of AUB were submitted and the results were analyzed. The youngest patient presenting with AUB was 21 years old, while the oldest was 77 years old. The most common complaint was menorrhagia in 201 (48.0%) out of 411 patients. The most common pathology finding in three groups was polyp in 100 (24.3%) cases. Hormonal effect was the next commonly observed pattern seen in 70 (17.0%) cases. P value was calculated as 0.003 which was significant using chi-square for the trend seen in age. Conclusion: Endometrial sampling is a useful tool for evaluation of women with AUB and referring patients for treatment. Histopathological evaluation of the endometrium is very useful in detecting the etiology of AUB. Transvaginal sonography has high sensitivity in detecting polyps.

In Silico Transcriptomic Analysis for Identification of Potential Diagnostic and Prognostic Biomarkers and Therapeutic Targets in Cervical Cancer using a Hybrid Genetic Algorithm–Support Vector Machine Approach

Background: Cervical cancer is the leading malignancy among women worldwide, posing clinical and public health challenges. This in silico study aims to identify potential diagnostic biomarkers, therapeutic targets, and prognostic markers associated with cervical cancer through integrative bioinformatics approaches. Methods: A hybrid machine learning approach, combining genetic algorithm (GA) and support vector machine (SVM), was applied to high-dimensional gene expression data from publicly available transcriptomic datasets, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 72 Geo samples (Affymetrix, Illumina) served as the primary dataset after normalization. Results: The GA-SVM model achieved about 99% accuracy and AUC with 10-fold cross validation, clearly separating cervical cancer from normal tissues. Eight genes (CXCL9, CTGF, ZNF704, ZEB2, SASH1, PTN, KPNA2, SLC5A1) were identified as diagnostic biomarkers. Protein-protein interaction (PPI) and functional enrichment analyses revealed 42 therapeutic targets (e.g. CDK1, BRCA1, CCNB1, and AURKB) linked to regulating cell cycle, DNA repair, and mitotic processes. Survival analysis identified six genes (CXCL1, DNMT1, MMP1, MYBL2, PCNA, and RRM2) as key prognostic markers. Additionally, transcription factor analysis identified E2F1 and TP63 as major regulators of the prognostic genes, elucidating the molecular mechanisms underlying cervical cancer progression. Conclusion: The identified gene signatures may serve as candidates for hypothesis generation and provide a computational framework to prioritize biomarkers and therapeutic targets in cervical cancer. However, these findings are based on in silico analyses and require experimental and clinical validation before translation into practice.

Prevalence of Human Papillomavirus (HPV) Genotypes among Women During 2015–2020 in Mashhad, Iran

Background: Cervical cancer is the fourth most common cancer in women, and human papillomavirus (HPV) is the leading cause of cervical cancer. Cervical cancer screening and HPV vaccination are important in the incidence of cervical cancer. Methods: This study was performed on Liquid Base Cytology (LBC) samples of 1214 women in Mashhad who were referred for cervical cancer screening in 2015-2020. Samples were examined by Single-Step PCR and Reverse Line Blot for HPV genotyping. Results: 386 women (31.8%) were HPV PCR positive. HPV genotyping of 277 samples showed that HPV 31 (3%), 16 (2.5%), 51 (2.2%), 18 (2%), and 66 (1.8%) were the most prevalent high-risk HPV (hrHPV) genotypes. Among low-risk HPV (lrHPV) genotypes, HPV 6 (9.2%), 53 (4.7%), and 42 (2.8%) were the most common genotypes. The range of multiple infections varied between two to eight genotypes and the prevalence of multiple HPV infections (12.4%) was higher than single infections (10.4%). For women with single HPV infections, HPV 31 and 66 were equally the most common hrHPV genotypes, followed by HPV 16 and 39. In women with multiple HPV infections, HPV 31 was the most common hrHPV genotype, followed by HPV 51 and 16. For both the single and multiple HPV infections, HPV 6 was the most common lrHPV genotype, followed by HPV 53 and 42. Conclusion: In conclusion, due to the high prevalence of HPV single and multiple infections, the need for governmentally supported HPV vaccination and through cervical cancer screening should be emphasized to prevent cervical cancer.

A New Model Including AMH Cut-off Levels to Predict Post-treatment Ovarian Function in Early Breast Cancer: A Prospective Cohort Study

Background: Breast cancer (BC) treatment decreases fertility capacity, but unnecessary fertility preservation procedures in women who would not be infertile after treatment would be a waste of time and resources and could cause the unwarranted exposure of cancer cells to exogenous sex hormones. It has been largely shown that post-treatment ovarian reserve is directly associated with pre-treatment anti-mullerian hormone levels (AMH0). A threshold for AMH0, or a model including AMH0 and patient characteristics that could distinguish the patients who will be infertile after treatments, still needs to be defined. Accordingly, this study was performed to specifically target this high-priority concern. Methods: Women≤45 years old with newly diagnosed non-metastatic BC were entered in this multicenter prospective cohort study. AMH0 and two-year post-treatment AMH (AMH2) were measured, and hormonal patient features were recorded as well. Receiver operating characteristic (ROC) curve analysis, decision tree (DT), and random forest analyses were performed to find a cut-off point for AMH0 and define a model involving related features for the prediction of AMH2. Results: The data from 84 patients were analyzed. ROC curve analysis revealed that AMH0>3 ng/mL (Area under the curve=0.69, 95% CI: 0.54‒0.84) was the best indicator for predicting AMH2≥0.7 (sensitivity=79%, specificity=60%). The best model detected by DT and random forest for predicting an AMH2>0.7 with a probability of 93% consisted of a combination of AMH0>3.3, menarche age<14, and age<31. Conclusion: This combination model can be used to withhold fertility preservation procedures in BC patients. Performing larger studies is suggested to further test this model.

Clinicopathological Evaluation of 15 Ectopic Adrenal Tissues

Ectopic adrenal tissue is a rare condition associated with embryological development defects seen in many different areas in the abdomen and pelvis. Here, we aimed to discuss the clinicopathological features of ectopic adrenal tissues diagnosed in our clinic, in light of the literature. We included cases of ectopic adrenal tissues incidentally detected in the specimens from patients undergoing operation for various diagnoses during 2012- March 2020. The cases were examined according to gender, age, location and accompanying pathological diagnoses. During this period, 15 cases of ectopic adrenal tissues (6 paratubal, 3 paraovarian, 2 paratesticular, 1 spermatic cord, 1 paraaortic, 1 liver capsule, 1 omentum) were detected accompanied by two endometrial carcinomas, two serous cystadenomas, one seminoma, one mixed germ cell tumor, one bilateral ovarian serous carcinoma and hepatic high-grade colon adenocarcinoma metastasis. In this report, the fifth ectopic adrenal tissue accompanying a malignant testicular tumor, the fifth and sixth ectopic adrenal tissues occurring with ovarian serous cystadenoma, the first case observed with serous cystadenocarcinoma and the first case detected with hepatic adenocarcinoma metastasis are presented. Our cases are mostly women and adult men. Ectopic adrenal tissues can lead to hormonal problems and also to adrenal cortex and medulla neoplasms. Microscopically, they may be confused with clear cell gynecological and germ cell tumors. If the ectopic focus is misdiagnosed as an implant, a benign entity may be incorrectly reported as malignant. Also, it is important to prevent mis-staging in malignancies. For precise diagnosis, an immunopanel such as inhibin, melan A, and calretinin can be performed.

Uterine and Cervical Cancer in Iran: An epidemiologic analysis of the Iranian National Population-Based Cancer Registry

Background: Gynecologic cancers, including neoplasms of the cervix and uterine, are the fourth most common malignancies, causing 3.46% of deaths in women aged 15 to 59. Objectives: We aimed to report the Iranian National Population-based Cancer Registry (INPCR) results for Cervical and Uterine cancers in 2017. Methods: The total population of Iran in 2017 was 80881792. INPCR collected data on cervical and uterine cancer incidence from 31 provinces of Iran. In this project, we retrospectively examined all the country’s regions in terms of screening for the existence of these two cancers. The registry data bank in Iran was used. Results: Overall, 3481 new cervical and uterine cancer cases were registered in INPCR, including 842 cases of cervical cancer (with a crude rate of 1.04) and 2639 cases of uterine cancer (with a crude rate of 3.26). The average age-standardized incidence rate (ASR) was 0.99 for cervical cancer and 3.29 for uterine cancer. Out of 3481 new cervical and uterine cancer cases, 2887 were registered with pathological findings and 594 without pathological confirmation. In cervical cancers, the highest rate was related to squamous cell carcinoma, with 486 cases (57.72%). Conclusion: Our results showed that Iran is a low-risk area for the incidence of cervical and uterine cancers. In this study, the highest rate of cervical cancer was related to squamous cell carcinoma, confirming previous reports. However, this rate was lower than previous studies and suggested an increase in other types of cervical cancer in Iran.

Trends in the Incidence Rates of Breast and Gynecological Cancers in Asia from 1998–2012: An Ecological Study

Background: There is limited evidence on the epidemiology and time trend analysis of incidence rates of gynecological cancer in Asia as a whole. We conducted this study to demonstrate breast and gynecological cancers incidence and trends in selected Asian populations. Method: We conducted this ecological study using cancer and population data from cancer incidence in five continents (CI5). We extracted the data of breast, uterine, cervix and ovary cancers in selected Asian populations from 1998 to 2012 from CI5plus. We used Joinpoint regression model (version 4.8.0.1) to evaluate the annual percentage change (APC), which characterizes trends in cancer rates over time, and the average annual percent changes (AAPCs), which describes the average APCs over a period of multiple years. Results were considered statistically significant at P < 0.05. Results: Between breast and gynecological cancers, breast cancer has the highest incidence rates among women in Asia. The time trend of the incidence rates showed a constant growth in breast, ovary and corpus uteri cancers. This rising trend was obviously sharper for uterine cancer (AAPC 95% CI = 3.4 [3.0, 3.7]) followed by breast [AAPC 95% CI = 2.1 (2.0, 2.2)] and ovarian cancers (AAPC 95% CI = 0.5 [-0.4, 1.3]). The age-adjusted incidence rate (ASR) of cervical cancer displayed a declining trend from 1998 to 2012 (AAPC 95% CI = -1.4 [-2.4, -0.5]). Conclusion: Incidence rates of breast and gynecological cancers have a rising trend in Asian countries. However, breast and gynecological cancers have different patterns of time trend.

Epidemiological Study of Various HPV Strains in Cervical Fluid Samples in South-Eastern Iran, 2018–2020

Background: Uterine cervical malignancy is one of the commonly detected malignancies related to the human papillomavirus (HPV) and is increasing incidentally in developing countries. Therefore, the use of an efficient diagnostic method is required as an effectual step for cervical cancer prevention and treatment. The purpose of the study was to diagnose various types of HPV in the cervical cytology specimens in the South-East of Iran. Methods: This cross-sectional study was performed on 1079 cervical fluid cytology specimens referred for two years, between 2018-2020. Polymerase chain reaction (PCR) and hybridization (INNO-LiPA HPV Genotyping EXTRA II assay) were used to determine HPV DNA and their genotypes, respectively. Results: HPV was positive in 37.7% (407 of 1079) patients with a mean age of 34.62 ± 8.82. Among positive cases, 252 (62%) had only one HPV genotype and 155 (38.05%) had multiplex HPV genotypes, which included 94 (60.7%), 38 (24.6%), 18 (11.6%) and 5 (3.2%) cases with two, three, four and five or more genotypes, respectively. The samples with multiple strains revealed 31 HPV genotypes with the four most prevalent being HPV6 (14.7%), HPV16 (10.9%), HPV53 (9.6%) and HPV51 (5.9%). Conclusion: HPV infection is the main health challenge for women that requires improved health service programs and appropriate epidemic vaccination.

Cost-Effectiveness of HPV vaccination; Need for Economic and Social Policy Intervention