RARE DISEASE
Vulvar squamous cell carcinoma
Vulvar squamous cell carcinoma
Vulvar squamous cell carcinoma
Synonyms: Squamous cell carcinoma of the vulva
Synonyms: Squamous cell carcinoma of the vulva
Synonyms: Squamous cell carcinoma of the vulva
Drug discovery
0
drugs
With orphan designations
Overview
Vulvar squamous cell carcinoma (VSCC) is the most common vulvar malignancy (90% of cases), arising via HPV-associated or HPV-independent pathways (lichen sclerosus/chronic inflammation) [1][4][5]. It predominantly affects postmenopausal women (median age 65–69) and presents with pruritus, lesions, or ulcerations [1][2][9]. Treatment prioritizes surgical resection, with adjuvant radiotherapy/chemotherapy for advanced stages, while targeted therapies (EGFR inhibitors, anti-VEGF) and immunotherapy show emerging potential [3][7][15].
Therapies
Surgery: Radical local excision or vulvectomy ± sentinel lymph node biopsy (gold standard for localized disease) [1][7][15].
Adjuvant therapy: Radiation ± chemotherapy for node-positive/advanced disease; neoadjuvant chemoradiation for unresectable tumors [7][15].
Targeted/immunotherapy: Erlotinib (EGFR inhibitor), bevacizumab (VEGF inhibitor), and pembrolizumab (PD-1 inhibitor) in recurrent/metastatic settings [3][7].
Categories: rare gynecological and obstetric diseases, rare neoplastic diseases
Research Papers
930 drug discovery papers about Vulvar squamous cell carcinoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
930 drug discovery papers about Vulvar squamous cell carcinoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-01 | Inhibition of Plasminogen Activator Inhibitor-1 (PAI-1) by Tiplaxtinin Attenuates the Aggressive Phenotype of Vulvar Squamous Cell Carcinoma Cells In Vitro.
Vulvar squamous cell carcinoma (VSCC), while relatively rare, is associated with significant morbidity. Activation of G-protein coupled estrogen receptor 1 (GPER1), which has a tumor-suppressing effect in VSCC, leads to reduced expression of plasminogen activator inhibitor-1 (PAI-1). PAI-1, a key regulator of the plasminogen activation system, is overexpressed in various cancers and is linked to poor prognosis. Its role and potential as a therapeutic target in VSCC remain poorly explored. This study investigated the effects of the specific PAI-1 inhibitor tiplaxtinin (PAI-039, TPX) on the aggressive behavior of VSCC cells in vitro. Expression of PAI-1 was verified by western blot. The effects of TPX treatment on viability, proliferation, migration, and invasion of A431 and Cal-39 VSCC cells were assessed using AlamarBlue, crystal violet, gap closure, and Boyden chamber assays, respectively. Apoptosis was examined using the Annexin V/propidium iodide (PI) assay. Both VSCC cell lines showed PAI-1 expression. With increasing TPX concentrations, viability and proliferation of the VSCC cells decreased significantly. Cell migration and invasion were both significantly reduced under treatment with the PAI-1 inhibitor. Apoptosis was not significantly induced by TPX. PAI-1 inhibitor TPX showed a strong inhibitory effect on VSCC cells, significantly reducing their viability, proliferation, migration and invasive capacity. This compound showed a strong ability to suppress important cell functions associated with cancer progression, making it a promising candidate for VSCC therapy to specifically inhibit growth and spread of VSCC.
2026-06-19 | Use of the dual tyrosine kinase inhibitor lapatinib for the treatment of vulvovaginal squamous cell carcinoma in a dog.
Vulvovaginal squamous cell carcinoma (SCC) is an uncommon neoplasm in dogs. An 11-year-old female spayed German Shepherd dog presented with a history of excessive peri-vulvar grooming and a 3 cm × 3 cm irregular mass involving the vagina and vulva. Incisional biopsy confirmed a diagnosis of primary vulvovaginal SCC. Abdominal ultrasonography and thoracic radiographs indicated no evidence of systemic or regional metastasis. Surgical excision and adjuvant radiation therapy were declined, and the patient was treated with lapatinib, an orally administered dual tyrosine kinase inhibitor. Treatment resulted in a partial response within 1 month and complete resolution of the primary lesion within 3 months. No recurrence of the initial lesion was observed after 1 year of treatment despite development of perivulvar cutaneous lesions that were not associated with clinical signs. Lapatinib was well tolerated but did result in acute hepatic injury that was resolved using hepatoprotective antioxidant medication and intermittent treatment cessation.
2026-06-18 | Advanced Squamous Cell Carcinoma of the Vulva (FIGO IIIb): Clinical Presentation, Imaging and Multidisciplinary Management
Background: Squamous cell carcinoma of the vulva is a rare malignancy accounting for less than 5% of gynecological cancers. In locally advanced stages (FIGO III–IVA), the prognosis remains poor, particularly when surgical resection is not feasible. Case Presentation: We report the case of a 69-year-old woman presenting with a moderately differentiated, keratinizing and infiltrating squamous cell carcinoma of the vulva, classified as FIGO IIIb, with large bilateral necrotic inguinal lymphadenopathy. Pelvic MRI revealed a tissue process measuring 62 × 39 × 20 mm and inguino-perineal lymph nodes reaching 47 × 60 mm. The multidisciplinary team decided on neoadjuvant concurrent chemoradiotherapy (CCRT) with curative intent. The course was unfavorable, with the patient dying during a hospitalization for metabolic complications and tumor-related infection. Conclusion: This case illustrates the diagnostic and therapeutic challenges of locally advanced vulvar cancer and underlines the importance of early detection and prompt multidisciplinary management.
2026-06-17 | Field Cancerization of the Cervix and Vulva in a Young HIV-Positive Woman: Diagnostic Challenges in Multifocal HPV Disease - A Case Report and Literature Review.
Human Papillomavirus (HPV) is a well-established cause of cancers of the cervix, vulva, and vagina, particularly high-risk types such as HPV-16 and 18. In women living with HIV, impaired immune function reduces viral clearance, leading to persistent infection, faster progression of precancerous lesions, and involvement of multiple sites within the lower genital tract. This phenomenon is often explained by the concept of "field cancerization", where widespread HPV exposure results in synchronous neoplastic changes in adjacent mucosal tissues. A 36-year-old HIV-positive woman presented with abnormal vaginal bleeding and post-coital bleeding. Testing revealed infection with multiple high-risk HPV genotypes, including HPV-16, and cervical cytology showed High-grade Squamous Intraepithelial Lesion (HSIL). Histopathological evaluation confirmed two concurrent HPV-related lesions: invasive squamous cell carcinoma of the cervix (FIGO stage IB1) and vulvar HSIL (VIN 3). She underwent a radical hysterectomy with pelvic lymph-node dissection along with wide local excision of the vulvar lesion, followed by adjuvant pelvic radiotherapy. This case illustrates the uncommon coexistence of cervical squamous cell carcinoma and vulvar HSIL in an HIV-positive woman, emphasizing the role of immunosuppression in persistent HPV infection and multifocal disease. Thorough evaluation of the entire lower genital tract, along with vigilant follow-up, is crucial for early detection and improved outcomes in this high-risk population.
2026-06-17 | A clinically concordant vulvar cancer patient-derived xenograft model retaining primary molecular signature for preclinical drug sensitivity assessment.
Establish and validate a patient-derived xenograft (PDX) model for vulvar cancer (VC). Evaluate the efficacy of commonly used clinical drugs both in vitro and in vivo using this model. Fresh primary vulvar cancer tumor tissues were then subcutaneously implanted into the scapular regions of immunodeficient mice, with tumor formation monitored and recorded in these mice. Hematoxylin and eosin (H&E) staining was performed to observe and compare the histopathological features of the primary and xenograft tumors, while immunohistochemical (IHC) staining was used to assess the consistency of protein expression profiles between the primary and xenograft tumors. Polymerase chain reaction (PCR) methods were employed to confirm the human origin of the xenograft tumors. Finally, the sensitivity of guideline-recommended chemotherapy drugs was evaluated using both HDST and in vivo efficacy studies, aiming to validate the drug responses observed in vitro with those seen in vivo. Tumor tissue from a primary vulvar squamous cell carcinoma patient was successfully transplanted into the subcutaneous region of mice and stably passed to the fourth generation. H&E staining results showed that the PDX model retained the atypia and original histological features of the primary tumor cells. IHC staining further confirmed that the protein expression profile of the xenograft tumors in the PDX model was consistent with that of the primary tumor. PCR humanization identification confirmed that the tumor tissues were of human origin. HDST drug screening results, combined with in vivo efficacy experiments, validated the sensitivity of the PDX model to guideline-recommended chemotherapy drugs, demonstrating clinical consistency. We have successfully established a vulvar cancer PDX model. This model retains the fundamental molecular characteristics of the primary human vulvar cancer tumor, thus offering an advantageous approach for preclinical assessment of novel therapies and investigation into the disease's pathogenesis.
2026-07-01 | Inhibition of Plasminogen Activator Inhibitor-1 (PAI-1) by Tiplaxtinin Attenuates the Aggressive Phenotype of Vulvar Squamous Cell Carcinoma Cells In Vitro.
Vulvar squamous cell carcinoma (VSCC), while relatively rare, is associated with significant morbidity. Activation of G-protein coupled estrogen receptor 1 (GPER1), which has a tumor-suppressing effect in VSCC, leads to reduced expression of plasminogen activator inhibitor-1 (PAI-1). PAI-1, a key regulator of the plasminogen activation system, is overexpressed in various cancers and is linked to poor prognosis. Its role and potential as a therapeutic target in VSCC remain poorly explored. This study investigated the effects of the specific PAI-1 inhibitor tiplaxtinin (PAI-039, TPX) on the aggressive behavior of VSCC cells in vitro. Expression of PAI-1 was verified by western blot. The effects of TPX treatment on viability, proliferation, migration, and invasion of A431 and Cal-39 VSCC cells were assessed using AlamarBlue, crystal violet, gap closure, and Boyden chamber assays, respectively. Apoptosis was examined using the Annexin V/propidium iodide (PI) assay. Both VSCC cell lines showed PAI-1 expression. With increasing TPX concentrations, viability and proliferation of the VSCC cells decreased significantly. Cell migration and invasion were both significantly reduced under treatment with the PAI-1 inhibitor. Apoptosis was not significantly induced by TPX. PAI-1 inhibitor TPX showed a strong inhibitory effect on VSCC cells, significantly reducing their viability, proliferation, migration and invasive capacity. This compound showed a strong ability to suppress important cell functions associated with cancer progression, making it a promising candidate for VSCC therapy to specifically inhibit growth and spread of VSCC.
2026-06-19 | Use of the dual tyrosine kinase inhibitor lapatinib for the treatment of vulvovaginal squamous cell carcinoma in a dog.
Vulvovaginal squamous cell carcinoma (SCC) is an uncommon neoplasm in dogs. An 11-year-old female spayed German Shepherd dog presented with a history of excessive peri-vulvar grooming and a 3 cm × 3 cm irregular mass involving the vagina and vulva. Incisional biopsy confirmed a diagnosis of primary vulvovaginal SCC. Abdominal ultrasonography and thoracic radiographs indicated no evidence of systemic or regional metastasis. Surgical excision and adjuvant radiation therapy were declined, and the patient was treated with lapatinib, an orally administered dual tyrosine kinase inhibitor. Treatment resulted in a partial response within 1 month and complete resolution of the primary lesion within 3 months. No recurrence of the initial lesion was observed after 1 year of treatment despite development of perivulvar cutaneous lesions that were not associated with clinical signs. Lapatinib was well tolerated but did result in acute hepatic injury that was resolved using hepatoprotective antioxidant medication and intermittent treatment cessation.
2026-06-18 | Advanced Squamous Cell Carcinoma of the Vulva (FIGO IIIb): Clinical Presentation, Imaging and Multidisciplinary Management
Background: Squamous cell carcinoma of the vulva is a rare malignancy accounting for less than 5% of gynecological cancers. In locally advanced stages (FIGO III–IVA), the prognosis remains poor, particularly when surgical resection is not feasible. Case Presentation: We report the case of a 69-year-old woman presenting with a moderately differentiated, keratinizing and infiltrating squamous cell carcinoma of the vulva, classified as FIGO IIIb, with large bilateral necrotic inguinal lymphadenopathy. Pelvic MRI revealed a tissue process measuring 62 × 39 × 20 mm and inguino-perineal lymph nodes reaching 47 × 60 mm. The multidisciplinary team decided on neoadjuvant concurrent chemoradiotherapy (CCRT) with curative intent. The course was unfavorable, with the patient dying during a hospitalization for metabolic complications and tumor-related infection. Conclusion: This case illustrates the diagnostic and therapeutic challenges of locally advanced vulvar cancer and underlines the importance of early detection and prompt multidisciplinary management.
2026-06-17 | Field Cancerization of the Cervix and Vulva in a Young HIV-Positive Woman: Diagnostic Challenges in Multifocal HPV Disease - A Case Report and Literature Review.
Human Papillomavirus (HPV) is a well-established cause of cancers of the cervix, vulva, and vagina, particularly high-risk types such as HPV-16 and 18. In women living with HIV, impaired immune function reduces viral clearance, leading to persistent infection, faster progression of precancerous lesions, and involvement of multiple sites within the lower genital tract. This phenomenon is often explained by the concept of "field cancerization", where widespread HPV exposure results in synchronous neoplastic changes in adjacent mucosal tissues. A 36-year-old HIV-positive woman presented with abnormal vaginal bleeding and post-coital bleeding. Testing revealed infection with multiple high-risk HPV genotypes, including HPV-16, and cervical cytology showed High-grade Squamous Intraepithelial Lesion (HSIL). Histopathological evaluation confirmed two concurrent HPV-related lesions: invasive squamous cell carcinoma of the cervix (FIGO stage IB1) and vulvar HSIL (VIN 3). She underwent a radical hysterectomy with pelvic lymph-node dissection along with wide local excision of the vulvar lesion, followed by adjuvant pelvic radiotherapy. This case illustrates the uncommon coexistence of cervical squamous cell carcinoma and vulvar HSIL in an HIV-positive woman, emphasizing the role of immunosuppression in persistent HPV infection and multifocal disease. Thorough evaluation of the entire lower genital tract, along with vigilant follow-up, is crucial for early detection and improved outcomes in this high-risk population.
2026-06-17 | A clinically concordant vulvar cancer patient-derived xenograft model retaining primary molecular signature for preclinical drug sensitivity assessment.
Establish and validate a patient-derived xenograft (PDX) model for vulvar cancer (VC). Evaluate the efficacy of commonly used clinical drugs both in vitro and in vivo using this model. Fresh primary vulvar cancer tumor tissues were then subcutaneously implanted into the scapular regions of immunodeficient mice, with tumor formation monitored and recorded in these mice. Hematoxylin and eosin (H&E) staining was performed to observe and compare the histopathological features of the primary and xenograft tumors, while immunohistochemical (IHC) staining was used to assess the consistency of protein expression profiles between the primary and xenograft tumors. Polymerase chain reaction (PCR) methods were employed to confirm the human origin of the xenograft tumors. Finally, the sensitivity of guideline-recommended chemotherapy drugs was evaluated using both HDST and in vivo efficacy studies, aiming to validate the drug responses observed in vitro with those seen in vivo. Tumor tissue from a primary vulvar squamous cell carcinoma patient was successfully transplanted into the subcutaneous region of mice and stably passed to the fourth generation. H&E staining results showed that the PDX model retained the atypia and original histological features of the primary tumor cells. IHC staining further confirmed that the protein expression profile of the xenograft tumors in the PDX model was consistent with that of the primary tumor. PCR humanization identification confirmed that the tumor tissues were of human origin. HDST drug screening results, combined with in vivo efficacy experiments, validated the sensitivity of the PDX model to guideline-recommended chemotherapy drugs, demonstrating clinical consistency. We have successfully established a vulvar cancer PDX model. This model retains the fundamental molecular characteristics of the primary human vulvar cancer tumor, thus offering an advantageous approach for preclinical assessment of novel therapies and investigation into the disease's pathogenesis.
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Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
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