Highlights
- Early detection of vulvar cancer significantly improves survival rates and clinical outcomes.
- Awareness and education on vulvar cancer symptoms are crucial for timely diagnosis and prevention.
Summary and Overview
Vulvar cancer affects the external female genitalia and has been rising by about 14% in some high-income countries. Key risk factors include HPV infection, smoking, chronic inflammation, and immunosuppression such as HIV. Early detection is difficult due to subtle symptoms often mistaken for benign conditions. Diagnosis involves clinical examination and biopsy, supported by imaging and emerging molecular tests like methylation assays. Treatment is multidisciplinary, mainly surgical, with adjunct radiation, chemotherapy, and targeted therapies based on tumor and patient factors. Despite advances, screening and prevention guidelines remain limited, highlighting the need for ongoing research. Increased public and professional awareness, HPV vaccination, and management of precursor lesions are crucial for prevention and improved outcomes.
Signs, Symptoms, and Diagnosis
Early vulvar cancer may be asymptomatic or present with persistent itching, skin color changes, lumps, or pain, often confused with benign conditions. Symptoms also include bleeding, tenderness, dysuria, and vulvar burning. Vulvar melanomas and verrucous carcinoma have distinct appearances like pigmented lesions or wart-like growths. Diagnosis typically occurs between ages 60-80 and involves physical examination, biopsy (punch, excisional, or incisional), and imaging (CT, MRI, PET) for staging and lymph node assessment. Sentinel lymph node biopsy reduces morbidity compared to full lymphadenectomy. Molecular diagnostics, including methylation marker panels, show promise in risk prediction and management.
Causes and Pathophysiology
Vulvar cancer arises mainly via HPV infection and chronic vulvar inflammation. HPV-associated high-grade squamous intraepithelial lesions (HSIL) and HPV-independent differentiated VIN linked to lichen sclerosus are precursors. Genetic alterations such as PIK3CA mutations define molecular subtypes influencing carcinogenesis. Rare inherited disorders like Fanconi anemia and hereditary cancer syndromes (Lynch, Peutz-Jeghers) may elevate risk indirectly. These molecular insights support development of targeted diagnostics and therapies.
Treatment
Surgery is the primary treatment for vulvar cancer, often combined with radiation for squamous cell carcinoma. Advanced cases may receive chemoradiation or neoadjuvant chemotherapy to preserve anatomy. Biologic therapies like topical imiquimod are used for early lesions. Staging by FIGO and AJCC systems guides treatment. Emerging targeted therapies address specific genetic mutations (e.g., HER2, NTRK), and biomarker testing may personalize neoadjuvant chemotherapy and other treatments.
Prognosis
Prognosis depends on stage, histology, and molecular markers. Early-stage localized cancer has about 86% five-year survival, dropping to around 30% with metastasis. Molecular markers such as methylation status of ZNF582, SST, and miR124-2 in high-grade VIN predict progression risk. Vulvar cancer typically progresses slowly, allowing a treatment window if detected early. Prognosis varies individually based on health, tumor features, and treatment response.
Prevention and Awareness
Prevention focuses on managing precursor lesions like vulvar intraepithelial neoplasia and HPV vaccination, which reduces vulvar cancer risk. Public and professional education is vital as early symptoms are often subtle or mistaken for benign conditions, leading to delayed diagnosis. Awareness campaigns encourage prompt evaluation of persistent vulvar symptoms to improve outcomes. Healthcare guidelines promote prevention, early detection, and referral but require further refinement.
Research and Future Directions
Ongoing research emphasizes molecular profiling, biomarkers, and advanced imaging to improve diagnosis, staging, and personalized treatment. Validated methylation markers aid early detection and prognosis. CT and MRI, including radiomic analysis, support noninvasive assessment of treatment response. Emerging biologic and immunotherapies target molecular pathways driving vulvar cancer. Though hereditary mutations are less common in vulvar cancer, their role in risk stratification remains under study. Continued multidisciplinary research aims to enhance prevention, diagnosis, and tailored therapies.
The content is provided by Harper Eastwood, Scopewires
