Patients with human papillomavirus (HPV)-negative vulvar cancer commonly harbored TP53 mutations, according to results from a whole-exome analysis published in Gynecological Oncology. Mutations in other cancer-associated genes were also identified.

Currently, the treatment of vulvar cancer is not based on molecular pathologic information. According to the authors, individual cases “could additionally benefit from molecular pathological information [to] guide the therapeutic extent of primary treatment.” The purpose of this study was to characterize the mutation pattern of this disease.

The study included 34 patients with vulvar cancer with matching specimens of tumor and normal vulvar tissue. Pathologic studies were conducted by a gynecopathologist. DNA whole-exome next-generation sequencing was performed on the matching tissue specimens to identify molecular aberrations including missense mutations and copy number alterations.

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Sequencing identified integration of viral E7 gene from HPV 16 among 35.3% of samples; the remaining were HPV-negative. The median number of cancer-related mutations per sample was 41.5. There was no association between mutation burden and HPV status.

The most common nonsynonymous mutations observed was in the TP53 gene, which was detected in 56% of samples. TP53 mutations were mutually exclusive of the presence of HPV (P <.0001).

The other most common nonsynonymous mutations occurred in some cancer-related genes that were novel to vulvar cancer, and included NBPF1 (20.6%), MACF1 (14.7%), DOCK2 (11.8%), and MAP2 (11.8%). Common nonsynonymous mutations were identified in known vulvar cancer-associated genes included SYNE2 (14.7%), KMT2D (11.8%), PIK3CA (11.8%), SYNE1 (11.8%), FBXW7 (8.8%), NSD1 (8.8%), and CDKN2A (5.9%). There was no significant difference in frequency of these mutations and HPV status.

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CNAs were analyzed in 26 samples. Overall, the most common gains occurred in chromosomes 3q, 5p, and 8q, whereas the most common losses were of chromosomes 3p, 11q, and X. Gain of chromosome 11q13.2-q13.3 occurred more frequently among the HPV-negative compared with the HPV-positive samples, which spans the known cancer-related GAL, CPT1A, and MRPL21 genes.

The authors called their study “a first step in analyzing molecular patterns in vulvar cancer,” and acknowledged that “validation of the presented dat in a larger cohort, including transcriptomic and proteomic analysis for further subtype characterization and prediction of treatment response as well as prognosis are highly desirable.”


Prieske K, Alawi M, Oliveira-Ferrer L, et al. Genomic characterization of vulvar squamous cell carcinoma [published online June 24, 2020]. Gynecologic Oncol. doi: 10.1016/j.ygyno.2020.06.482