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. 2024 Jun;484(6):985-994.
doi: 10.1007/s00428-023-03690-8. Epub 2023 Nov 8.

Prognostic value of HPV-PCR, p16 and p53 immunohistochemical status on local recurrence rate and survival in patients with vulvar squamous cell carcinoma

A W Pouwer  1 , N C Te Grootenhuis  2 , F Hinten  1 , G H de Bock  3 , A G J van der Zee  4 , W J G Melchers  5 , M H M Oonk  4 , J A de Hullu  1 , H Hollema  6 , J Bulten  7
Affiliations

Prognostic value of HPV-PCR, p16 and p53 immunohistochemical status on local recurrence rate and survival in patients with vulvar squamous cell carcinoma

A W Pouwer et al. Virchows Arch. 2024 Jun.

Abstract

The primary aim of this study was to assess the association between human papilloma virus (HPV) and p53 expression and local recurrence (LR), disease specific survival (DSS), and overall survival (OS) in patients with vulvar squamous cell carcinoma (VSCC). Secondary, the accuracy of p16 immunohistochemistry for HPV status was assessed. The tumor tissue of 255 patients, surgically treated for primary unifocal VSCC between 2000 and 2010, was analyzed. HPV-PCR and P16 and p53 immunohistochemical stainings were performed. All histologic slides were independently reviewed by two expert gyneco-pathologists. Time to first LR, DSS, and OS for the variables p16, p53, and HPV-PCR were compared using univariable and multivariable Cox-regression analyses. In 211/255 (83.5%) patients, HPV-PCR was negative. The local recurrence rate was significantly lower in patients positive with HPV-PCR (10-year LR rate 24.6%) versus negative tumors (47.5%), p = 0.004. After multivariable analyses, this difference remained significant (HR 0.23 (95% CI 0.08-0.62) p = 0.004). There was no difference in LR rate correlated to the p53 expression. DSS and OS did not significantly differ after multivariable analyses for all different subgroups. Sensitivity and specificity of p16 staining for presence of HPV detected by HPV-PCR were 86.4% and 93.8%, respectively. In conclusion, patients with HPV-negative VSCCs have significantly more LR compared to patients with HPV-positive VSCCs, and p16 immunohistochemistry is a reliable surrogate marker for HPV status. No relevant subgroup for LR or survival based on HPV/p53 status could be identified. We advise to perform an HPV-PCR or p16 IHC staining in all patients with VSCC.

Keywords: HPV; Local recurrence; Survival; Vulvar carcinoma; p16; p53.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart regarding HPV, p16 and p53 status of the tumors; VSCC vulvar squamous cell carcinoma
Fig. 2
Fig. 2
Local recurrence by HPV status; LogRank p = 0.004. HR 0.36 (95% CI 0.17–0.74 p = 0.006). Adjusted for age, FIGO stage, depth of invasion, growth pattern, and p53 status HR 0.23 (95% CI 0.08–0.62 p = 0.004)
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