Molecular classification of vulval cancer: Comparing pre-surgical biopsy and surgical specimen of radical vulvectomy from the same patients

Background Classification of vulvar carcinoma (VCX) into one of the three molecular subtypes has significant prognostic and therapeutic impact. An HPV-associated lesion that is p16 positive and p53 wild type represents improved prognosis compared to other subtypes. HPV-independent VCX, mostly associated with lichen sclerosus is characterized by TP53-alteration (i.e. aberrant p53-expression) and p16 non-aberrant staining. A third (minor) subtype is characterized by normal staining for both markers. It has been shown that patients with p53-aberrant tumors may benefit from more radical surgical approach. Contrary, HPV-high risk associated VCA (with p16-block positivity) represent better response to chemoradiation.

The aim of this study was to determine the concordance of molecular subtyping on diagnostic biopsy compared to the surgical resection specimen.

Methods 56 matched pairs of VCA diagnostic biopsies (Bx) and its surgical resection specimens (vulvectomies) were immunohistochemically evaluated for the immunoexpression of p16 and p53 using the criteria recommended by the International Society of Gynecological Pathologists (ISGyP), the British Association of Gynecological Pathologists and the LAST-Project. Doubtful immunohistochemical staining results were molecularly analysed for HPV-DNA and/or TP53-mutation. The molecular results of the resection specimens were used as "gold standard". The examination of the Bx were blinded to the findings within the resection specimen.

Results Matched pair analysis represented a high agreement for molecular subtyping of VCX comparing diagnostic Bx and the surgical resection specimen: 93.7% (16/17 cases) for the p16+/p53wt cases; 94.4% (34/36) for p16-/p53mut. Within the p16- /p53wt VCX there was a lower concordance (50%; 2/4 cases).

Conclusion There is a high concordance rate (~94%) between diagnostic Bx and surgical resection specimen for the two major types within the molecular classification of VCX using immunoexpression of p53 (as a surrogate marker for TP53-alterations) and p16 (as a surrogate marker for HPV high-risk infection).

These results may represent a valuable finding within the clinical setting for treatment decisions. By accurate subtyping of the VCX before curative treatment, the prognostically best treatment approach can be chosen for the patients.

So, molecular subtyping of VCX within diagnostic biopsies represents a robust tool to tailor the treatment approach of patients with VCX.

Publikationsverlauf

Artikel online veröffentlicht:
21. Juni 2023