Significance of p53 and presence of differentiated vulvar intra-epithelial neoplasia (dVIN) at resection margin in early stage human papillomavirus-independent vulvar squamous cell carcinoma

Emily F Thompson; Kathryn Shum; Richard W C Wong; Giorgia Trevisan; Janine Senz; Jutta Huvila; Samuel Leung; David G Huntsman; C Blake Gilks; Jessica N McAlpine; Lynn Hoang; Amy Jamieson

doi:10.1136/ijgc-2022-003763

Significance of p53 and presence of differentiated vulvar intra-epithelial neoplasia (dVIN) at resection margin in early stage human papillomavirus-independent vulvar squamous cell carcinoma

Int J Gynecol Cancer. 2022 Sep 13:ijgc-2022-003763. doi: 10.1136/ijgc-2022-003763. Online ahead of print.

Authors

Affiliations

¹ Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada.
² Department of Pathology, United Christian Hospital, Hong Kong, Hong Kong.
³ Department of Pathology, Barts Health NHS Trust, London, London, UK.
⁴ Department of Pathology, University of Turku, Turku, Finland.
⁵ Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
⁶ Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
⁷ Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada [email protected].

PMID: 36100281
DOI: 10.1136/ijgc-2022-003763

Abstract

Objective: Vulvar squamous cell carcinoma and in situ lesions can be stratified by human papillomavirus (HPV) and TP53 status into prognostic risk groups using p16 and p53 immunohistochemistry. We assessed the significance of vulvar squamous cell carcinoma resection margin positivity for either differentiated vulvar intra-epithelial neoplasia (dVIN) or abnormal p53 immunohistochemistry, and other pathologic variables, in a cohort of patients with HPV-independent (HPV-I) p53 abnormal (p53abn) vulvar squamous cell carcinomas.

Methods: Patients with stage I-II HPV-I p53abn vulvar squamous cell carcinoma with negative invasive margins who did not receive adjuvant radiation from a single institution were included. Tumors underwent margin reassessment using p53 immunohistochemistry. Cases were segregated into (1) morphologic dVIN at margin; or (2) abnormal p53 immunohistochemistry staining at margin without morphologic dVIN (p53abn immunohistochemistry); or (3) margins negative by morphology and p53 immunohistochemistry. Clinicopathologic/outcome data were collected.

Results: A total of 51 patients were evaluated: (1) 12 with dVIN on margin; (2) 12 with p53abn immunohistochemistry on margin without morphologic dVIN; and (3) 27 with margins negative for morphologic dVIN and p53abn immunohistochemistry. The recurrence rate for patients with dVIN or p53abn immunohistochemistry on the margin was equally high at 75% each, compared with 33% with margins negative for morphologic dVIN and p53abn immunohistochemistry (p=0.009). On multivariate analysis, positive in situ margins maintained an association with disease recurrence (p=0.03) whereas invasive margin distance (radial and deep), lymphovascular invasion, and tumor size did not.

Conclusions: Patients with stage I-II HPV-I vulvar squamous cell carcinoma with margins positive for either dVIN or p53abn immunohistochemistry without morphologic dVIN showed increased disease recurrence, regardless of invasive margin distance. These findings show that p53 immunohistochemistry is a useful adjunct for evaluating margin status in HPV-I vulvar squamous cell carcinoma and may support repeat excision for positive in situ margins (dVIN or p53abn immunohistochemistry).

Keywords: Vulva.