Molecular events in the pathogenesis of vulvar squamous cell carcinoma

Xing, Deyin; Fadare, Oluwole

doi:10.1053/j.semdp.2020.09.010

Cited by 20 publications

(18 citation statements)

References 155 publications

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“…11 Recent studies on molecular heterogeneity in vulvar carcinogenesis demonstrated that the risk of vHSIL progressing into VSCC seems to be correlated with the extent of chromosomal alterations; in particular, a gain of chromosome 1pq seems to be associated with HPV-positive lesions. 33,34 There are no formal screening strategies for VSCC, but early identification is essential to optimize treatment outcomes. [35][36][37][38] Vulvar malignancies may coexist with or be initially misdiagnosed as an infectious or inflammatory condition, delaying diagnosis.…”

Section: Vulvar Squamous Cell Carcinoma and Precancerous Lesionsmentioning

confidence: 99%

Vulvar High-Grade Squamous Intraepithelial Lesions and Cancer as a Risk Factor for Anal Cancer: A Review

Albuquerque

Stockdale

Heller

et al. 2022

J Low Genit Tract Dis

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Anal squamous cell carcinoma (ASCC) has a higher incidence described in certain groups, namely, in women with vulvar high-grade squamous intraepithelial lesions (vHSILs) and/or human papillomavirus squamous cell carcinoma (VSCC). This review describes terminology, vHSIL, and VSCC in their association with ASCC and the published recommendations for early detection of this cancer in these women. Materials and Methods:A narrative review was conducted by the authors on vHSIL and VSCC as risk factors for ASCC. Results:The ASCC and VSCC incidence are increasing. Women with vHSIL and/or VSCC can present with ASCC at diagnosis, being one of the highest-risk groups. Suspicious symptoms include rectal bleeding, pain, and a sensation of an anal mass. Digital anorectal examination can help detect early ASCC. Sensitivity of anal cytology in women with vHSIL and VSCC seems low, with the exception of immunosuppressed women with genital neoplasia (cervix, vagina, and vulva). There are still insufficient data on high-resolution anoscopy in women with vHSIL and/or VSCC as a screening method.Conclusions: Clinicians need be aware that women with vHSIL and VSCC comprise one of the highest-risk groups for ASCC. Inquiring suggestive symptoms of ASCC and a digital anorectal examination can help in the early detection of this type of cancer.

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Section: Vulvar Squamous Cell Carcinoma and Precancerous Lesionsmentioning

confidence: 99%

Vulvar High-Grade Squamous Intraepithelial Lesions and Cancer as a Risk Factor for Anal Cancer: A Review

Albuquerque

Stockdale

Heller

et al. 2022

J Low Genit Tract Dis

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“…Abnormal expressions of PTEN/AKT/mTOR have been found in GCs, which are hypothesized to be the pathway involved in cancer occurrence, leading to out-of-control cell proliferation and metabolism and resistance to apoptosis [20]. Some clinical trials investigating the role of different mTOR inhibitors also indicated that targeting mTOR alone could lead to unsatisfactory outcomes in GC [28].…”

Section: Abnormal Expression Of Pten/akt/mtor In Gynecological Cancersmentioning

confidence: 99%

“…In vulvar cancer, as a downstream component of the AKT cascade, mTOR was found to be widely expressed in most vulvar cancer samples in immunohistochemical staining [28]. In vitro experiments showed that mTOR inhibitors of rapamycin, everolimus and AZD2014 could significantly inhibit the proliferation of vulva cancer cell lines of cellosaurus-39 (CAL-39) and SW-954 [44].…”

Section: Abnormal Expression Of Pten/akt/mtor In Gynecological Cancersmentioning

confidence: 99%

PTEN gene and AKT/mTOR pathway in gynecological cancers and cancer immune escape

2022

European Journal of Gynaecological Oncology

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Gynecological cancers (GCs) include cervical, uterine, ovarian, vulvar and vaginal cancer. For women in China, 2 of the 10 most common cancers are GCs (8th: cervical cancer, incidence rate: 3.96%; 10th: ovarian cancer, incidence rate: 2.91%). These cancers can lead to enormous psychological and economic burdens. Phosphatase and tensin homolog (PTEN) gene and protein kinase B (AKT) and mammalian target of rapamycin (mTOR) pathway are widely involved in the development of GCs, and an imbalance in regulatory T cells (Treg) in the cancer micro-environment mediated by PTEN and AKT/mTOR pathway was shown to lead to cancer cell immune escape, growth and metastasis. Considering that the pathogenesis of PTEN and AKT/mTOR pathway in GCs and cancer immune escape remains unclear, this review article intends to provide an update in this field. We made a comprehensive search of several databases, including Web of Science, MEDLINE, Ovid and Cochrane Database of Systematic Reviews, was conducted from inception to March 2022. The search strategy included the combinations of the following medical terms: gynecological cancers, cervical cancer, uterine cancer, ovarian cancer, vulvar cancer, vaginal cancer, PTEN gene, AKT/mTOR pathway, and cancer immune escape. We found that currently the mechanism of the PTEN gene and AKT/mTOR pathway in GCs is not fully clear. However, the activation of the AKT/mTOR signaling pathway and imbalance of Treg cell in the micro-environment caused by the function loss of PTEN is involved in the occurrence and development of GCs, and related to the prognosis of patients. This review article presented the latest research progress on the PTEN gene and AKT/mTOR pathway in GCs and cancer cell immune escape.

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“…The introduction of HPV vaccination is expected to partially reduce the incidence of squamous vulvar cancers within the next twenty years [5]. Alternative pathways involved in vulvar cancer pathogenesis arise from chronic dermatoses as lichen sclerosus or planus [6]. Less frequent histologies, in about 10% of cases, are basal cell carcinoma, melanoma, Paget's disease, Bartholin gland adenocarcinoma, neuroendocrine tumors and sarcomas.…”

Section: Introductionmentioning

confidence: 99%

Role of Chemotherapy in Vulvar Cancers: Time to Rethink Standard of Care?

Mazzotta

Pizzuti

Krasniqi

et al. 2021

Cancers

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The actual role of chemotherapy in vulvar cancer is undeniably a niche topic. The low incidence of the disease limits the feasibility of randomized trials. Decision making is thus oriented by clinical and pathological features, whose relevance is generally weighted against evidence from observational studies and clinical practice. The therapeutic management of vulvar cancer is increasingly codified and refined at an individual patient level. It is of note that the attitude towards evidence sharing and discussion within a multidisciplinary frame is progressively consolidating. Viable options included in the therapeutic armamentarium available for vulvar cancer patients are frequently an adaption from standards used for cervical or anal carcinoma. Chemotherapy is more frequently combined with radiotherapy as neo-/adjuvant or definitive treatment. Drugs commonly used are platinum derivative, 5-fluorouracil and mitomicin C, mostly in combination with radiotherapy for radiosensitization. Exclusive chemotherapy in the neo-/adjuvant setting comprises platinum-derivative, combined with bleomicin and methotrexate, 5-fluorouracil, ifosfamide or taxanes. In advanced disease, current regimens include cisplatin-based chemoradiation, with or without 5-fluorouracil, or doublets with platinum in combination with a taxane. Our work is also enriched by a concise excursus on the biologic pathways underlying vulvar cancer. Introductory hints are also provided on targeted agents, a rapidly evolving research field.

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Molecular events in the pathogenesis of vulvar squamous cell carcinoma

Cited by 20 publications

References 155 publications

Vulvar High-Grade Squamous Intraepithelial Lesions and Cancer as a Risk Factor for Anal Cancer: A Review

Vulvar High-Grade Squamous Intraepithelial Lesions and Cancer as a Risk Factor for Anal Cancer: A Review

PTEN gene and AKT/mTOR pathway in gynecological cancers and cancer immune escape

Role of Chemotherapy in Vulvar Cancers: Time to Rethink Standard of Care?

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