Human papillomavirus infection mediates response and outcome of vulvar squamous cell carcinomas treated with radiation therapy

Horne, Zachary D.; Dohopolski, Michael; Pradhan, Dinesh; Bhargava, Rohit; Edwards, Robert P.; Kelley, Joseph L.; Comerci, John T.; Olawaiye, A.B.; Courtney‐Brooks, Madeleine; Bockmeier, M.M.; Berger, Jessica; Taylor, S.E.; Sukumvanich, Paniti; Beriwal, Sushil

doi:10.1016/j.ygyno.2018.08.002

Cited by 36 publications

(22 citation statements)

References 31 publications

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“…Recently published data support the concept that p16 positivity may be a good prognostic indicator for radiotherapy response in patients with vulvar cancer [40,41], as has been shown earlier for HPV-positive oropharyngeal cancers [18]. Our study was not designed to make a definitive comment regarding radiotherapy, and our number of patients receiving radiotherapy was small.…”

Section: Discussionsupporting

confidence: 52%

The Clinical Relevance of p16 and p53 Status in Patients with Squamous Cell Carcinoma of the Vulva

Barlow

Lambie

Donoghoe

et al. 2020

Journal of Oncology

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Objective. To investigate the prognostic significance of HPV status in vulvar squamous cell carcinomas (VSCC) and to determine whether preoperative determination of p16 or p53 status would have clinical relevance. Methods. Patients treated for VSCC at a tertiary hospital in Sydney, Australia, from 2002 to 2014, were retrospectively evaluated (n = 119). Histological specimens were stained for p53 and p16 expression, and HPV status was determined by PCR detection of HPV DNA. Results. HPV DNA was detected in 19%, p16 expression in 53%, and p53 expression in 37% of patients. Kaplan–Meier survival estimates indicated that p16/HPV-positive patients had superior five-year disease-free survival (76% versus 42%, resp., p=0.004) and disease-specific survival (DSS) (89% versus 75% resp., p=0.05) than p53-positive patients. In univariate analysis, nodal metastases (p<0.001), tumor size >4 cm (p=0.03), and perineural invasion (p=0.05) were associated with an increased risk of disease progression and p16 expression with a decreased risk (p=0.03). In multivariable analysis, only nodal metastases remained independent for risk of disease progression (p=0.01). For DSS, lymph node metastases (p<0.001) and tumor size (p=0.008) remained independently prognostic. Conclusion. The p16/HPV and p53 status of VSCC allows separation of patients into two distinct clinicopathological groups, although 10% of patients fall into a third group which is HPV, p16, and p53 negative. p16 status was not independently prognostic in multivariable analysis. Treatment decisions should continue to be based on clinical indicators rather than p16 or p53 status.

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Section: Discussionsupporting

confidence: 52%

The Clinical Relevance of p16 and p53 Status in Patients with Squamous Cell Carcinoma of the Vulva

Barlow

Lambie

Donoghoe

et al. 2020

Journal of Oncology

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“…A number of studies have suggested that HPV-associated VSCC is more radiosensitive than HPV-independent VSCC. 23,29,30 This is a particularly plausible hypothesis, given that the same differential sensitivity to radiation has been shown for head and neck squamous cell carcinomas. 51,52 Given that the HPV-independent carcinomas are associated with a worse prognosis and are therefore more likely to receive radiotherapy, it is particularly important to address this issue.…”

Section: Impact Of Hpv Status On Treatmentmentioning

confidence: 67%

“…With the recognition of the prognostic significance of HPV status in patients with invasive VSCC, the question arises of whether this information can be used to guide treatment and improve patient outcomes. A number of studies have suggested that HPV‐associated VSCC is more radiosensitive than HPV‐independent VSCC . This is a particularly plausible hypothesis, given that the same differential sensitivity to radiation has been shown for head and neck squamous cell carcinomas .…”

Section: Impact Of Hpv Status On Treatmentmentioning

confidence: 94%

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Vulval squamous cell carcinoma and its precursors

2019

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Vulval squamous cell carcinoma (VSCC) can arise through two distinct pathways [human papillomavirus (HPV)‐associated and HPV‐independent], and these VSCC variants are recognised as different disease entities on the basis of different aetiologies, morphological features, molecular events during oncogenesis, precursor lesions, prognosis, and response to treatment. The precursor of HPV‐associated VSCC, variously referred to as high‐grade squamous intraepithelial lesion (HSIL) [vulvar intraepithelial neoplasia (VIN) 2/3] or usual‐type VIN, is morphologically identical to the more common HSIL (cervical intraepithelial neoplasia 2/3) of the cervix. The precursor lesions of HPV‐independent VSCC include differentiated VIN, differentiated exophytic vulvar intraepithelial lesion, and vulvar acanthosis with altered differentiation; these have been under‐recognised by pathologists in the past, leading to delays in treatment. This review will discuss the recent advances in diagnostic surgical pathology of VSCC and its precursors, and how these diagnoses can impact on patient management.

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“…According to the 4th WHO classification, the prognostic impact of the HPV status is still considered to be unclear (Del Pino et al 2013). However, indications increase that HPV-association is a positive predictive factor for SCCVs (Lee et al 2016;Horne et al 2018). Regarding oropharyngeal squamous cell cancer, several studies could verify p16 as a reliable surrogate marker for HPV-association (Prigge et al 2017;Ma and Lewis 2012;Tan et al 2016).…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

Czogalla

Pham

Trillsch

et al. 2020

J Cancer Res Clin Oncol

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Aim Programmed death-ligand 1 (PD-L1) has become a widely used predictive biomarker for therapy with checkpoint inhibitors in a variety of cancers. Here, we studied the expression of PD-L1 in squamous cell carcinomas of the vulva (SCCV) with regard to HPV status via its surrogate marker p16. Additionally, the status of PD-L1 and p16 were analyzed for prognostic information and potential correlation to tumor-infiltrating lymphocytes (TILs). Methods PD-L1 was analyzed in 128 cases of SCCV using the tumor proportion score (TPS), the immune cell score (ICS) and the combined positive score (CPS). Cases were immunostained for p16 and analyzed for stromal TILs. PD-L1, p16, and TILs were compared to clinico-pathological parameters and patient's survival. Results TPS ≥ 50% and CPS ≥ 50 were correlated to a worse grading (p = 0.028 and p = 0.031), but not to FIGO-stage. CPS ≥ 50 was associated to a worse prognosis with overall survival (p = 0.021) but was not correlated to the progression-free survival. P16-positivity was correlated to a longer progression-free survival (p = 0.006) and overall survival (p = 0.023). PD-L1 expression was independent from p16 status. TILs ≥ 50% were present in 24% of the cases and were strongly correlated to PD-L1 (TPS p = 0.02, ICS p < 0.001, CPS p = 0.001). Conclusion Our data demonstrate that PD-L1 expression is frequent in SCCV and independent from p16 status. High PD-L1 expression was associated with an unfavorable outcome whereas p16-positivity turned out to be an independent positive prognostic factor.

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Human papillomavirus infection mediates response and outcome of vulvar squamous cell carcinomas treated with radiation therapy

Cited by 36 publications

References 31 publications

The Clinical Relevance of p16 and p53 Status in Patients with Squamous Cell Carcinoma of the Vulva

The Clinical Relevance of p16 and p53 Status in Patients with Squamous Cell Carcinoma of the Vulva

Vulval squamous cell carcinoma and its precursors

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

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