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International Journal of Gynaecology... Aug 2023Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009....
INTRODUCTION
Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies.
METHODS
The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system.
RESULTS
Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. Stage II (IIA): non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. Stage III (IIIA): differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. Stage IV (IVA): locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification (POLEmut, MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or POLEmut status in Stages I and II, this results in upstaging or downstaging of the disease (IICm or IAm ).
SUMMARY
The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data.
Topics: Female; Humans; Peritoneal Neoplasms; Neoplasm Staging; Endometrial Neoplasms; Prognosis; Carcinoma, Endometrioid; Retrospective Studies
PubMed: 37337978
DOI: 10.1002/ijgo.14923 -
Journal of Gynecologic Oncology Sep 2023Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009....
INTRODUCTION
Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies.
METHODS
The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system.
RESULTS
Based on the existing evidence, the substages were defined as follows: non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification (, MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or status in Stages I and II, this results in upstaging or downstaging of the disease (IICm or IAm).
SUMMARY
The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data.
Topics: Female; Humans; Peritoneal Neoplasms; Endometrial Neoplasms; Endometrium; Uterus; Carcinoma, Endometrioid
PubMed: 37593813
DOI: 10.3802/jgo.2023.34.e85 -
Medicine May 2024The human papillomavirus (HPV) belongs to the Papillomaviridae family of viruses which includes small, double-stranded DNA viral agents. Approximately 90% of HPV... (Review)
Review
The human papillomavirus (HPV) belongs to the Papillomaviridae family of viruses which includes small, double-stranded DNA viral agents. Approximately 90% of HPV infections occur asymptomatically and resolve spontaneously. However, infection with high-risk viral strains can lead to the development of preneoplastic lesions, with an increased propensity to become cancerous. The location of these malignancies includes the oral cavity, cervix, vagina, anus, and vulva, among others. The role of HPV in carcinogenesis has already been demonstrated for the aforementioned neoplasia. However, regarding skin malignancies, the mechanisms that pinpoint the role played by HPV in their initiation and progression still elude our sight. Until now, the only fully understood mechanism of viral cutaneous oncogenesis is that of human herpes virus 8 infection in Kaposi sarcoma. In the case of HPV infection, however, most data focus on the role that beta strains exhibit in the oncogenesis of cutaneous squamous cell carcinoma (cSCC), along with ultraviolet radiation (UVR) and other environmental or genetic factors. However, recent epidemiological investigations have highlighted that HPV could also trigger the onset of other non-melanocytic, for example, basal cell carcinoma (BCC), and/or melanocytic skin cancers, for example, melanoma. Herein, we provide an overview of the role played by HPV in benign and malignant skin lesions with a particular focus on the main epidemiological, pathophysiological, and molecular aspects delineating the involvement of HPV in skin cancers.
Topics: Humans; Skin Neoplasms; Papillomavirus Infections; Papillomaviridae; Carcinoma, Squamous Cell; Carcinoma, Basal Cell; Melanoma; Human Papillomavirus Viruses
PubMed: 38787972
DOI: 10.1097/MD.0000000000038202 -
Journal of Cancer Research and... 2023Carcinoma cervix is the fourth most commonly diagnosed cancer worldwide, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Carcinoma cervix is an...
BACKGROUND
Carcinoma cervix is the fourth most commonly diagnosed cancer worldwide, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Carcinoma cervix is an uncommon malignancy in Kashmir. In this retrospective study, we have tried to find clinicopathological characteristics of carcinoma cervix along with the survival rates at our tertiary care hospital.
MATERIALS AND METHODS
Case records of cervical cancer patients registered from January 1, 2015, to January 1, 2019, were retrieved. A total of 138 patients was registered. 22 had undergone surgery, and out of these 17 had received postoperative radiotherapy. 109 patients were treated with definitive chemoradiation and 13 with palliative radiotherapy. Descriptive statistics were used to summarize patient and treatment-related variables, and Kaplan-Meier analysis was performed for survival analysis.
RESULTS
A total of 138 cases that were registered from 2015 to 2019 were included in this study. The median age at the presentation was 56 years. Most of the patients had a performance status of 1 (98 patients (71.01)). Most of the patients 110 (79.71%) were married before 20 years of age, only 1 patient was unmarried, and 85 (61.59) patients were multiparous in our study group. Only 14 (10.14%) patients in our study group had a history of oral contraceptive use and most of them were non-smokers [124 (89.80%)]. Multiple marriages were present in 8 (5.79%) patients only. The most common presenting symptom was bleeding per vagina (78.26%), and the maximum number of patients fall in the post-menopausal group (67.39%). 116 patients had squamous cell carcinoma histology while 10 patients had adenocarcinoma histology. Most of the patients had stage II and stage III disease (85 patients). At last, follow up out of 138 patients 75 (54.35) were alive. 3 year disease-free survival was 54.34% and 3-year overall survival was 72.46%.
CONCLUSION
Carcinoma cervix is an uncommon malignancy in Kashmir because of different socio-cultural and religious practices but the response to treatment, toxicity profile, and survival are similar to the rest of the world.
Topics: Female; Humans; Middle Aged; Uterine Cervical Neoplasms; Cervix Uteri; Retrospective Studies; Carcinoma, Squamous Cell; Chemoradiotherapy; Neoplasm Staging
PubMed: 37787316
DOI: 10.4103/jcrt.jcrt_203_22 -
European Review For Medical and... Oct 2023Human papillomavirus (HPV), which is known to play a very important role in genital area (vulva, vagina, and cervix) cancers in women, is responsible for almost all...
OBJECTIVE
Human papillomavirus (HPV), which is known to play a very important role in genital area (vulva, vagina, and cervix) cancers in women, is responsible for almost all cervical cancers. However, a significant proportion of cervical carcinomas (approximately 7%) is HPV-negative. Therefore, there are still two important questions to be answered: 1. Why is HPV Deoxyribonucleic acid (DNA) not found in all cervical carcinomas? 2. Are HPV-DNA-negative cervical cancers a specific subgroup of cervical cancers with different biological behavior (worse prognosis)? In this article, we aimed to evaluate the clinicopathological characteristics and survival of patients with confirmed HPV-negative tumors in order to answer these two questions.
PATIENTS AND METHODS
A total of 97 patients who underwent HPV-DNA testing and received a histological diagnosis of cervical cancer were included in the study. 14 HPV-DNA negative and 83 HPV-DNA positive cervical carcinoma patients were detected. Demographic profiles, clinicopathological characteristics, progression-free, and overall survival of all patients were analyzed.
RESULTS
Women with HPV-negative tumors were diagnosed at an older age range (p=0.05), and their demographic data other than age range were similar to HPV-positive tumors. P16 staining pattern was not observed in any of the HPV-negative tumors (p=0.001), and a positive P53 staining pattern was detected in 35.7% of the HPV-negative tumors. Although disease-free survival (PFS) (p=0.224) and overall survival (OS) (p=0.219) were worse in the HPV-negative patient group, this difference was not statistically significant.
CONCLUSIONS
HPV-negative cervical cancers do not have a poor prognosis unlike their counterparts in other anatomical regions where HPV-associated tumors are present.
Topics: Humans; Female; Uterine Cervical Neoplasms; Papillomavirus Infections; Prognosis; Disease-Free Survival; Human Papillomavirus Viruses; DNA, Viral; Papillomaviridae
PubMed: 37843334
DOI: 10.26355/eurrev_202310_33948 -
Journal of Contemporary Brachytherapy Dec 2023To compare dose volume parameters of target and organs at risk in vaginal vault brachytherapy using ovoids or cylinder in post-operative endometrial carcinoma.
PURPOSE
To compare dose volume parameters of target and organs at risk in vaginal vault brachytherapy using ovoids or cylinder in post-operative endometrial carcinoma.
MATERIAL AND METHODS
The study was done among 25 histologically proven post-operative endometrial carcinoma patients requiring vaginal brachytherapy. All patients underwent both cylinder and ovoids application alternatively on weekly basis. Ovoids size ranged from 2 to 3 cm diameter. Diameters of cylinder ranged between 2.5 and 3.5 cm. Bladder, rectum, urethra, and clinical target volume (CTV) were contoured on CT simulation images. Prescribed dose was 6-7 Gy in 2-3 fractions at 0.5 cm from the surface of applicator.
RESULTS
The mean values of D, D, V, V, V, and V of CTV were comparable between cylinder and ovoids plans. The mean dose of CTV was significantly higher with cylinder than with ovoids, and D was significantly higher with ovoids (mean = 15.63 Gy vs. 14.64 Gy, = 0.016, and D = 37.82% vs. 42.86%, = 0.042, for cylinder vs. ovoids). In the dosimetry of the vault, D, D, V, V, V, and mean of the vault did not show any significant difference between cylinder and ovoids. The V was significantly higher with cylinder plans than ovoids, and D of the vault was significantly higher with ovoids plans (V = 14.81% vs. 6.86%, = 0.02, and D = 37.77% vs. 44.80%, = 0.029, for cylinder vs. ovoids). D, D, D, and mean for the bladder, rectum, and urethra were comparable between the cylinder and ovoid plans.
CONCLUSIONS
The present study showed that the dose to organs at risk, most of the dosimetric parameters of CTV, and vault were comparable between the cylinder and ovoid plans. Both applicators provide good reproducibility. The choice of applicator will ultimately depend on the institutional policies and oncologist decision. However, in patients with dog-ear configuration of the vagina, ovoids may be preferred as per ABS guidelines.
PubMed: 38230405
DOI: 10.5114/jcb.2023.134171 -
Menopause (New York, N.Y.) Aug 2023Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). (Meta-Analysis)
Meta-Analysis
Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis.
IMPORTANCE
Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA).
OBJECTIVE
The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe.
EVIDENCE REVIEW
Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses.
FINDINGS
A total of 44 controlled trials met the eligibility criteria ( N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment.
CONCLUSIONS AND RELEVANCE
Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.
Topics: Female; Humans; Dyspareunia; Vagina; Hyperplasia; Bayes Theorem; Network Meta-Analysis; Vulva; Atrophy; Tamoxifen; Selective Estrogen Receptor Modulators; Vaginal Diseases; Endometrial Neoplasms
PubMed: 37369079
DOI: 10.1097/GME.0000000000002211