Vulvar Squamous Cell Carcinoma (VSC)

Overview

Vulvar squamous cell carcinoma (VSC) is a squamous malignancy arising from the vulvar epithelium. Two distinct etiologic pathways exist: HPV-associated tumors (HPV-positive, typically younger patients) and HPV-independent tumors arising on a background of lichen sclerosus or differentiated vulvar intraepithelial neoplasia (HPV-negative, older patients). VSC is a rare gynecologic cancer; approximately one-third of patients experience recurrence with limited therapeutic options.

Cohorts in the corpus

  • vsc_cuk_2018 — 15 Korean vulvar SCC patients (6 HPV+, 9 HPV-) profiled by whole-exome sequencing at The Catholic University of Korea; first genome-wide landscape of this tumor type PMID:29422544.

Recurrent alterations

  • HPV(-) vulvar SCC recurrently harbors TP53, CDKN2A, and HRAS mutations plus 7p and 8q gains and 2q loss; HPV(-) cases carried higher nonsilent and driver mutation loads than HPV(+) cases PMID:29422544.
  • HPV(+) vulvar SCC showed novel mutations in PIK3CA, BRCA2, and FBXW7 — none previously reported in this tumor type PMID:29422544.
  • PIK3CA and FAT1 were each altered in 40% (6/15) of vulvar SCCs irrespective of HPV status, making them the highest-frequency alterations in this cohort PMID:29422544.
  • Kataegis (localized hypermutation, inter-mutation distance ≤10 kb) was detected in 2 HPV(+) tumors; copy-neutral LOH was found in 4 tumors (1 HPV+, 3 HPV-) PMID:29422544.
  • Mutational signatures were compared against TCGA SCC cohorts (CESC, ESCA, HNSC, LUSC) and published CSCC/oral SCC datasets; CNA burden and signatures did not differ between HPV(+) and HPV(-) VSC subgroups PMID:29422544.

Subtypes

  • HPV-positive vulvar SCC: Associated with high-risk HPV types (HPV16, 52, 58 in the Korean WES cohort); carries lower mutation burden than HPV(-) cases; harbors PIK3CA, BRCA2, and FBXW7 mutations as novel genomic features PMID:29422544.
  • HPV-negative vulvar SCC: Arises independently of HPV; characterized by TP53, CDKN2A, and HRAS mutations plus recurrent 7p/8q gains and 2q loss; higher mutational and driver-mutation load than HPV(+) cases PMID:29422544.

Therapeutic landscape

  • No specific drug or targeted therapy has been established for VSC based on the corpus to date. The 40% prevalence of PIK3CA alterations across both HPV subgroups has been noted as a potential actionable target, though no clinical data from the corpus support a specific recommendation PMID:29422544.

Sources

  • PMID:29422544 — Han et al. (2018). First whole-exome sequencing landscape of vulvar squamous cell carcinoma (n=15, 6 HPV+, 9 HPV-, Korean cohort).

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