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Journal For Immunotherapy of Cancer Jan 2022Cemiplimab is a highly potent, hinge-stabilized human IgG4 monoclonal antibody (mAb) targeting programmed cell death 1 (PD-1) receptor approved for patients with locally...
Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) cemiplimab: ongoing and future perspectives in rare genital cancers treatment.
Cemiplimab is a highly potent, hinge-stabilized human IgG4 monoclonal antibody (mAb) targeting programmed cell death 1 (PD-1) receptor approved for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (SCC) who are not candidates for curative surgery or curative radiation. Recently, the phase 3 trial EMPOWER-Cervical 1 has investigated cemiplimab in patients with recurrent/metastatic cervical cancer. At interim analysis, overall survival (OS), progression free survival (PFS) and objective response rate (ORR) in overall and SCC populations favored cemiplimab over single agent chemotherapy. Cervical SCCs are the first for incidence among Human Papilloma Virus (HPV) related neoplasms and are highly correlated (about 95%) with the viral infection. Similarly, penile and vulvar SCC may develop on chronic HPV infections or on dermatological chronic conditions (ie, lichen). The molecular and viral similarities between external genital SCC and SCC originating from the cervical epithelium could be the rationale for using cemiplimab to treat locally advanced or metastatic penile and vulvar SCC as well. Some retrospective data have shown that cemiplimab may provide objective response and clinical benefit to some patients with penile or vulvar SCC and is overall safe to utilize in this population. Given the complexity of the immune activation and the considerable variability in tumor biology across patients and tumor types, the identification of biomarkers to warrant patient selection needs to be further explored. Ongoing clinical trials will hopefully shed light on the treatment paradigm of these rare tumors too, with special regard to the ideal combination and sequencing of immunotherapeutic strategies.
Topics: Antibodies, Monoclonal, Humanized; Genital Diseases; Humans; Immune Checkpoint Inhibitors; Neoplasms; Programmed Cell Death 1 Receptor; Rare Diseases
PubMed: 35101944
DOI: 10.1136/jitc-2021-003540 -
Journal of Clinical Medicine Feb 2021The aim of this study is to assess the projected incidence and prognostic indicators of gynecologic malignancies in the pediatric population. In this population-based...
The aim of this study is to assess the projected incidence and prognostic indicators of gynecologic malignancies in the pediatric population. In this population-based retrospective cohort study, girls ≤18 years with ovarian, uterine, cervical, vaginal and vulvar malignancies diagnosed between 2000 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER)-18 registry. The Kaplan-Meier method was used to analyze overall survival (OS). The age-adjusted annual incidence of gynecologic malignancies was 6.7 per 1,000,000 females, with neoplasms of the ovary accounting for 87.5%, vagina 4.5%, cervix 3.9%, uterus 2.5% and vulva 1.6% of all gynecologic malignancies. Malignant germ-cell tumors represented the most common ovarian neoplasm, with an increased incidence in children from 5-18 years. Although certain subtypes were associated with advanced disease stages, the 10-year OS rate was 96.0%. Sarcomas accounted for the majority of vaginal, cervical, uterine and vulvar malignancies. The majority of vaginal neoplasms were observed in girls between 0-4 years, and the 10-year OS rate was 86.1%. Overall, gynecologic malignancies accounted for 4.2% of all malignancies in girls aged 0-18 years and the histologic subtypes and prognosis differed significantly from patients in older age groups.
PubMed: 33673108
DOI: 10.3390/jcm10040722 -
Gynecologic Oncology Jan 2022The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly...
BACKGROUND
The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described.
PATIENTS AND METHODS
In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields.
RESULTS
The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months).
CONCLUSION
Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV- tumors.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Germany; Humans; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Vulvar Neoplasms; Young Adult
PubMed: 34794839
DOI: 10.1016/j.ygyno.2021.11.004 -
Modern Pathology : An Official Journal... Feb 2021Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC) is an aggressive clinical entity. Current diagnostic guidelines for premalignant lesions are...
Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC) is an aggressive clinical entity. Current diagnostic guidelines for premalignant lesions are ambiguous, and their molecular profile and progression events are still unclear. We selected 75 samples, from 40 patients, including 33 VSCC, 8 verrucous carcinomas (VC), 13 differentiated-type vulvar intraepithelial neoplasia (dVIN), 11 suspicious for dVIN (?dVIN), 6 differentiated exophytic vulvar intraepithelial lesions (DE-VIL), 2 vulvar acanthosis with altered differentiation (VAAD), and 2 usual-type vulvar intraepithelial neoplasia (uVIN/HSIL). Invasive and precursor lesions were matched in 29 cases. Clinical information, p16 immunohistochemistry, and mutation analysis were performed on all lesions. All dVIN, ?dVIN, DE-VIL, and VAAD were p16 negative, all uVIN/HSIL were p16 positive. In the HPV-independent group, mutations were identified in 6 genes: TP53 (n = 40), PIK3CA (n = 20), HRAS (n = 12), MET (n = 5), PTEN (n = 4), and BRAF (n = 1). TP53 mutations occurred in 73% (22/30) VSCC, 85% (11/13) dVIN, 70% (7/10) ?dVIN and no VC (0/8), DE-VIL (0/6) nor VAAD (0/2). Basal atypia was the only reliable feature of TP53 mutations. ?dVIN lesions that were non-acanthotic and atypical but obscured by inflammation, all harbored TP53 mutations. In lesions without TP53 mutations, PIK3CA (50% VC, 33% DE-VIL, 100% VAAD, 40% VSCC) and HRAS (63% VC, 33% DE-VIL, 0% VAAD, 20% VSCC) mutations were found. Mutational progression from in situ to invasive was seen (7/26, 27%) and usually involved TP53 (4/26, 15%). Cases with TP53 and PIK3CA co-mutations had the worse clinical outcomes (p < 0.001). We recommend testing for p53 in all HPV-independent lesions suspicious for dVIN, even in the presence of marked inflammation or non-acanthotic skin, particularly when close to a margin. VC, VAAD, and DE-VIL, were almost never mutated for TP53, but instead often harbored PIK3CA and HRAS mutations. In VSCC, combined TP53 and PIK3CA mutations may inform prognosis.
Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Papillomavirus Infections; Tumor Suppressor Protein p53; Vulvar Neoplasms
PubMed: 32792599
DOI: 10.1038/s41379-020-00651-3 -
Systematic Reviews Apr 2021Globally, cancer is generally recognized as a developmental threat yet most countries in Africa lack capacity to diagnose cancer especially gynecological cancers...
BACKGROUND
Globally, cancer is generally recognized as a developmental threat yet most countries in Africa lack capacity to diagnose cancer especially gynecological cancers resulting in late detection and poor outcomes. However, most studies on gynecological cancers in Africa tend to focus on cervical cancer compared to the other gynecological cancers. Therefore, this scoping review will aim to describe the existing literature on the epidemiological burden of ovarian, endometrial, vaginal, and vulva cancers, their risk factors, and potential screening methods/techniques in Africa to identify priority research gaps for further research to inform health policy decisions.
METHODS
The framework promulgated by Arksey and O'Malley and improved by Levac et al. will be used as a guide for this scoping review. A comprehensive search for relevant published studies in PubMed, CINAHL, SCOPUS, Google Scholar, and ScienceDirect with no date limitation to the last search date. The database search strategy will include keywords, Boolean operators, and medical subject heading terms. We will additionally consult the WHO/IARC website, IHME/Global Burden of Disease Study. A snowball approach will also be used to search the reference list of all included studies to obtain relevant papers for possible inclusion in this review. We will include articles that involve African countries, focused on ovarian, endometrial, vaginal, and vulva cancers, their risk factors, and potential screening methods/techniques in any language. We will exclude studies on cervical cancer and other cancers as well as review articles. The abstracts and full-text selection will be conducted by two independent reviewers using this review's eligibility criteria as a guide. All the review selection tools, and the data extraction form will be pilot tested for accuracy and consistency. The data will be organized into thematic areas, summarized and the results communicated narratively.
DISCUSSION
It is anticipated that this review will reveal important literature gaps to guide future research to inform health policy decisions about ovarian, endometrial, and rare gynecological neoplasms in Africa. This review's findings will be disseminated via peer review journals, conferences, and other social media such Twitter and LinkedIn.
Topics: Africa; Female; Humans; Research; Review Literature as Topic; Vulvar Neoplasms
PubMed: 33849664
DOI: 10.1186/s13643-021-01654-0 -
Journal of Cancer Research and Clinical... Aug 2023Vulvar cancer is the fourth most common malignancy of the female genital tract after endometrial, ovarian, and cervical carcinoma and affects mainly elderly women. In...
PURPOSE
Vulvar cancer is the fourth most common malignancy of the female genital tract after endometrial, ovarian, and cervical carcinoma and affects mainly elderly women. In 2020 there were registered more than 17,000 deaths worldwide related to vulvar carcinoma. Data about target-based therapies and predictive biomarkers for vulva carcinomas are rare so far. The metastasis-associated gene MTA1 is a transcriptional repressor with a potential effect on cancer. Expression of MTA1 was found to be significantly enhanced in gynecological malignancies as breast or ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of those tumor entities. Due to the lack of information around MTA1 and its significance regarding vulvar carcinoma, this study focuses on the expression of MTA1 in vulvar carcinoma and its correlation to clinicopathological characteristics and prognosis.
METHODS
A total of 157 paraffin-embedded vulvar cancer tissues were immunohistochemically stained and examined for MTA1 expression by using the immunoreactive score. Subsequently, the values were correlated with clinicopathological parameters.
RESULTS
MTA1 was found to be expressed in 94% of the patients in the cytoplasm and 91% in the nucleus. Cytoplasmatic expression of MTA1 was significantly increased in non-keratinizing squamous cell carcinoma and in vulvar carcinoma of the condylomatous type, compared to keratinizing squamous cell carcinoma and vulvar carcinoma of the verrucous type. High MTA1 expression in the nucleus was associated with advanced tumor size as well as higher FIGO grading. In addition, p16 negative vulvar carcinomas showed a higher nuclear expression of MTA1 compared to p16 positive vulvar carcinomas. Suprisingly, Kaplan-Meier analysis showed a significantly lower disease-free survival in tumor samples without a nuclear expression of MTA1.
CONCLUSIONS
MTA1 was identified as a negative prognostic marker for vulvar carcinoma associated with advanced tumor stage and FIGO grading. A possible explanation could be that the antibody used for this study does not bind to a possible mutation in the C terminal region of MTA leading to negative immunohistochemical staining and this can be correlated with early recurrence in patients with vulvar carcinoma.
Topics: Aged; Female; Humans; Biomarkers, Tumor; Carcinoma, Squamous Cell; Ovarian Neoplasms; Prognosis; Transcription Factors; Vulvar Neoplasms
PubMed: 36689059
DOI: 10.1007/s00432-023-04579-4 -
Journal of the American Academy of... May 2023
Topics: Female; Humans; Vulva; Vulvar Lichen Sclerosus; Laser Therapy; Vulvar Neoplasms; Carcinoma in Situ; Precancerous Conditions; Lichen Sclerosus et Atrophicus
PubMed: 36639033
DOI: 10.1016/j.jaad.2023.01.003 -
Vulvar cancer subclassification by HPV and p53 status results in three clinically distinct subtypes.Gynecologic Oncology Dec 2020There is great need for better risk stratification in vulvar squamous cell carcinoma (VSCC). Our aim was to define the prognostic significance of stratifying VSCC based...
OBJECTIVE
There is great need for better risk stratification in vulvar squamous cell carcinoma (VSCC). Our aim was to define the prognostic significance of stratifying VSCC based on p16 and p53 immunohistochemistry (IHC) as surrogate markers for HPV and TP53 mutations.
METHODS
A large retrospective cohort of surgically treated women with primary VSCC was used. VSCC were classified into three subtypes: HPV-positive (HPVpos), HPV-negative/p53 mutant (HPVneg/p53mut), and HPV-negative/p53 wildtype (HPVneg/p53wt). Overall survival (OS), relative survival (RS), and recurrence-free period (RFP) were depicted using the Kaplan-Meier method and survival curves for relative survival; associations were studied using univariable and multivariable Cox proportional hazard models.
RESULTS
Of the 413 VSCCs, 75 (18%) were HPVpos, 63 (15%) HPVneg/p53wt, and 275 (66%) HPVneg/p53mut VSCC. Patients with HPVneg/p53mut VSCC had worse OS and RS (HR 3.43, 95%CI 1.80-6.53, and relative excess risk (RER) of 4.02; 95%CI 1.48-10.90, respectively, and worse RFP (HR 3.76, 95%CI 2.02-7.00). HPVpos VSCC patients showed most favorable outcomes. In univariate analysis, the molecular subtype of VSCC was a prognostic marker for OS, RS and RFP (p = 0.003, p = 0.009, p < 0.001, respectively) and remained prognostic for RFP even after adjusting for known risk factors (p = 0.0002).
CONCLUSIONS
Stratification of VSCC by p16- and p53-IHC has potential to be used routinely in diagnostic pathology. It results in the identification of three clinically distinct subtypes and may be used to guide treatment and follow-up, and in stratifying patients in future clinical trials.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Clinical Decision-Making; Female; Humans; Middle Aged; Mutation; Neoplasm Recurrence, Local; Papillomaviridae; Papillomavirus Infections; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Tumor Suppressor Protein p53; Vulva; Vulvar Neoplasms; Vulvectomy; Young Adult
PubMed: 32972785
DOI: 10.1016/j.ygyno.2020.09.024 -
Dermatology Reports Nov 2022Vulvar malignant melanoma (VMM) is uncommon and poses a significant management challenge. Here, we presented a case of VMM managed by surgery, chemoradiation, and...
Vulvar malignant melanoma (VMM) is uncommon and poses a significant management challenge. Here, we presented a case of VMM managed by surgery, chemoradiation, and planned for targeted therapy. A 70- year-old woman with underlying diabetes mellitus and hypertension presented with a black-colored exophytic growth around her left vulva for two months. Initial biopsy confirmed malignant melanoma with positive staining for S100, HMB 45, and Melan A. An imaging study showed that the disease was localized to the vulva. She underwent bilateral radical vulvectomy and bilateral inguinofemoral lymph node dissection followed by radiotherapy. She had a locoregional disease recurrence, which was subsequently managed by palliative perineal radiotherapy, chemotherapy, and planned for immunotherapy. Vulvar malignant melanoma is a rare and aggressive tumor, with a poor overall prognosis, and high recurrence rate. Adjuvant chemotherapy, radiotherapy, and immunotherapy may be beneficial for local recurrence and distant metastasis cases. Molecular Analysis has a potential role in targeted therapy to improve the survival and outcome of the patient.
PubMed: 36483218
DOI: 10.4081/dr.2022.9345 -
American Journal of Obstetrics and... Feb 2021Women with gynecologic cancer face socioeconomic disparities in care that affect survival outcomes. The Affordable Care Act offered states the option to expand Medicaid...
BACKGROUND
Women with gynecologic cancer face socioeconomic disparities in care that affect survival outcomes. The Affordable Care Act offered states the option to expand Medicaid enrollment eligibility criteria as a means of improving timely and affordable access to care for the most vulnerable. The variable uptake of expansion by states created a natural experiment, allowing for quasi-experimental methods that offer more unbiased estimates of treatment effects from retrospective data than the traditional regression adjustment.
OBJECTIVE
To use a quasi-experimental, difference-in-difference framework to create unbiased estimates of impact of Medicaid expansion on women with gynecologic cancer.
STUDY DESIGN
We performed a quasi-experimental retrospective cohort study from the National Cancer Database files for women with invasive cancers of the uterus, ovary and fallopian tube, cervix, vagina, and vulva diagnosed from 2008 to 2016. Using a marker for state Medicaid expansion status, we created difference-in-difference models to assess the impact of Medicaid expansion on the outcomes of access to and timeliness of care. We excluded women aged <40 years owing to the suppression of the state Medicaid expansions status in the data and women aged ≥65 years owing to the universal Medicare coverage availability. Our primary outcome was the rate of uninsurance at diagnosis. Secondary outcomes included Medicaid coverage, early-stage diagnosis, treatment at an academic facility, and any treatment or surgery within 30 days of diagnosis. Models were run within multiple subgroups and on a propensity-matched cohort to assess the robustness of the treatment estimates. The assumption of parallel trends was assessed with event study time plots.
RESULTS
Our sample included 335,063 women. Among this cohort, 121,449 were from nonexpansion states and 213,614 were from expansion states, with 79,886 posttreatment cases diagnosed after the expansion took full effect in expansion states. The groups had minor differences in demographics, and we found occasional preperiod event study coefficients diverging from the mean, but the outcome trends were generally similar between the expansion and nonexpansion states in the preperiod, satisfying the necessary assumption for the difference-in-difference analysis. In a basic difference-in-difference model, the Medicaid expansion in January 2014 was associated with significant increases in insurance at diagnosis, treatment at an academic facility, and treatment within 30 days of diagnosis (P<.001 for all). In an adjusted model including all states and accounting for variable expansion implementation time, there was a significant treatment effect of Medicaid expansion on the reduction in uninsurance at diagnosis (-2.00%; 95% confidence interval, -2.3 to -1.7; P<.001), increases in early-stage diagnosis (0.80%; 95% confidence interval, 0.2-1.4; P=.02), treatment at an academic facility (0.83%; 95% confidence interval, 0.1-1.5; P=.02), treatment within 30 days (1.62%; 95% confidence interval, 1.0-2.3; P<.001), and surgery within 30 days (1.54%; 95% confidence interval, 0.8-2.3; P<.001). In particular, large gains were estimated for women living in low-income zip codes, Hispanic women, and women with cervical cancer. Estimates from the subgroup and propensity-matched cohorts were generally consistent for all outcomes besides early-stage diagnosis and treatment within 30 days.
CONCLUSION
Medicaid expansion was significantly associated with gains in the access and timeliness of treatment for nonelderly women with gynecologic cancer. The implementation of Medicaid expansion could greatly benefit women in nonexpansion states. Gynecologists and gynecologic oncologists should advocate for Medicaid expansion as a means of improving outcomes and reducing socioeconomic and racial disparities.
Topics: Adult; Black or African American; Cohort Studies; Early Detection of Cancer; Educational Status; Ethnicity; Female; Genital Neoplasms, Female; Health Policy; Hispanic or Latino; Humans; Medicaid; Medically Uninsured; Middle Aged; Neoplasm Staging; Non-Randomized Controlled Trials as Topic; Ovarian Neoplasms; Patient Protection and Affordable Care Act; Poverty; Propensity Score; Residence Characteristics; Retrospective Studies; Time-to-Treatment; United States; Uterine Cervical Neoplasms; Uterine Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms; White People
PubMed: 32777264
DOI: 10.1016/j.ajog.2020.08.007