Molecular heterogeneity in human papillomavirus-dependent and -independent vulvar carcinogenesis

Cancer Medicine
Dorian R A SwartsMaaike C G Bleeker

Abstract

Vulvar squamous cell carcinoma (VSCC) and precancerous vulvar intraepithelial neoplasia (VIN) can develop through human papillomavirus (HPV)-dependent and -independent pathways, indicating a heterogeneous disease. Only a minority of VIN progress, but current clinicopathological classifications are insufficient to predict the cancer risk. Here we analyzed copy number alterations (CNA) to assess the molecular heterogeneity of vulvar lesions in relation to HPV and cancer risk. HPV-status and CNA by means of whole-genome next-generation shallow-sequencing were assessed in VSCC and VIN. The latter included VIN of women with associated VSCC (VINVSCC ) and women who did not develop VSCC during follow-up (VINnoVSCC ). HPV-testing resulted in 41 HPV-positive (16 VINVSCC , 14 VINnoVSCC , and 11 VSCC) and 24 HPV-negative (11 VINVSCC and 13 VSCC) lesions. HPV-positive and -negative VSCC showed a partially overlapping pattern of recurrent CNA, including frequent gains of 3q and 8q. In contrast, amplification of 11q13/cyclinD1 was exclusively found in HPV-negative lesions. HPV-negative VINVSCC had less CNA than HPV-negative VSCC (P = .009), but shared chromosome 8 alterations. HPV-positive VINnoVSCC had less CNA than VINVSCC (P = .022). Inte...Continue Reading

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Citations

Jul 9, 2020·International Journal of Cancer. Journal International Du Cancer·Nikki B ThuijsMaaike C G Bleeker
Feb 10, 2019·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Paul A CohenJames Scurry
Apr 9, 2020·Infectious Agents and Cancer·Mario PretiTarik Gheit
Jul 16, 2020·International Journal of Molecular Sciences·Sebastian ZiębaMagdalena Kowalewska
Jan 12, 2021·International Journal of Cancer. Journal International Du Cancer·Nikki B ThuijsMaaike C G Bleeker
Oct 10, 2020·Seminars in Diagnostic Pathology·Deyin Xing, Oluwole Fadare
Jul 25, 2021·Cancers·Shatavisha DasguptaFolkert J van Kemenade
Oct 21, 2021·Journal of Lower Genital Tract Disease·Andreia AlbuquerquePedro Vieira-Baptista

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Methods Mentioned

BETA
dissection
PCR

Software Mentioned

ArrayExpress
CGHcall
R
WECCA
CGHtest
SPSS Statistics

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