p53 and p16ink4a As Predictive and Prognostic Biomarkers for Nodal metastasis and Survival in A Contemporary Cohort of Penile Squamous Cell Carcinoma

Mohanty, Sambit K.; Mishra, Sourav; Bhardwaj, Nitin; Sardana, Ruhani; Jaiswal, Sunil K.; Pattnaik, Niharika; Pradhan, Dinesh; Sharma, Saurabh; Kaushal, Seema; Baisakh, Manas; Das, S. N.; Pradhan, Manas Ranjan; Satapathy, Kaliprasad; Pattnaik, Ashis; Sharma, Shailendra; Khadenga, Chira R.; Das, Subodh K.; Rath, Debadarshi; Nanda, Biswajit; Parwani, Anil V.

doi:10.1016/j.clgc.2021.07.001

Cited by 14 publications

(7 citation statements)

References 40 publications

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“…In accordance with the findings of other European series [27], HPV-associated tumors represented a small percentage (29.5%) of all PSCC, which is in contrast with the findings of studies from sub-Saharan Africa or the Caribbean, which showed rates of HPV-associated PSCC as high as 80% [28]. As previously reported, p16 IHC results have shown excellent correlation with HPV ISH [29], reinforcing the validity of the recent WHO 2022 recommendation of using p16 IHC as a surrogate for the presence of high-risk HPV [22]. Our study revealed that the second type of PSCC defined by the WHO, HPV-independent tumors, includes at least two categories with different clinical and pathological features and, most importantly, a different prognosis.…”

Section: Discussionsupporting

confidence: 90%

p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas with Adverse Prognosis

Trias,

Algaba,

De Torres

et al. 2024

Preprint

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Background: Penile squamous cell carcinoma (PSCC) is classified into two prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. Conversely, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with prognosis in a large series of PSCC patients. p53 was analysed according to a recently described immunohistochemical (IHC) pattern-based framework that includes two normal (scattered, mid-epithelial) and four abnormal patterns (diffuse, basal overexpression, cytoplasmic and null) and closely correlates with TP53 mutational status. Methods: A total of 122 patients with surgically treated PSCC in three hospitals in Barcelona, Spain, were included. Based on HPV in situ hybridization and p16 and p53 IHC expression, the tumors were classified into three molecular types: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed for at least 22 months (median 56.9 months), and disease-specific survival (DSS) was analysed. Results: Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (p&lt;0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 patterns not recognized in the classical p53 IHC interpretation (basal, null, cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired DSS (hazard ratio=23.4, 95% confidence interval [CI]= 2.7-3095.3; p=0.001 and 16.3, 95% CI=1.8-2151.5; p=0.008, respectively). CONCLUSION: Compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define two prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

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Section: Discussionsupporting

confidence: 90%

p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas with Adverse Prognosis

Trias,

Algaba,

De Torres

et al. 2024

Preprint

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“…Among the studies included in our analysis, a total of twenty-nine studies reported HPV status. Out of these, eighteen studies employed the polymerase chain reaction (PCR) method for HPV detection [13,15,19,20,22,23,[25][26][27][28][31][32][33][35][36][37][38][39], six studies utilized in situ hybridization (ISH) [4,21,24,29,34,40], and four studies did not specify the method used for HPV detection [41][42][43][44]. Additionally, one study employed a Quantus fluorometer for the detection of HPV nucleic acid [30].…”

Section: Hpv Detection Methodsmentioning

confidence: 99%

“…Two different methodologies were employed for grading p16 on IHC. Six studies utilized a quantitative measurement approach, where the cut-off for considering a sample as p16-positive ranged from >10% to >75% of cells exhibiting positive staining [4,20,24,26,29,48]. Conversely, twelve studies employed subjective criteria to define p16 positivity, using descriptions such as strong and diffuse staining, vital staining of proliferative cells, continuous and complete cytoplasmic staining, intense confluent staining, or focal scattering of staining in the cytoplasm and nucleus of cells [13,19,[21][22][23]25,28,30,42,45,47,49].…”

Section: P16 Detection Methodsmentioning

confidence: 99%

“…Among the studies included in our analysis, Brazil and the United States both had the highest number of studies, with each country contributing eight studies (refer to Figure 2 for details). Fourteen studies reported on both HPV and p16 IHC status [4,13,[19][20][21][22][23][24][25][26][27][28][29][30], fifteen studies [15,[31][32][33][34][35][36][37][38][39][40][41][42][43][44] focused solely on HPV, and five studies [45][46][47][48][49] reported only on p16 status. For a summary of HPV and p16 positivity across the 34 included studies, please refer to Table 1 and Supplemental Table S2.…”

Section: Study Characteristicsmentioning

confidence: 99%

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The Prognostic Role of Human Papillomavirus and p16 Status in Penile Squamous Cell Carcinoma—A Systematic Review

Parza¹,

Mustasam

Ionescu

et al. 2023

Cancers

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PSCC is a rare cancer, with approximately half of all cases related to HPV. While HPV and p16 IHC testing have proven their prognostic value for oropharyngeal cancer, this is not yet established for PSCC. The current level of evidence exploring the relation between PSCC and HPV is moderate, so we conducted a systematic review following PRISMA guidelines to evaluate the prognostic role of HPV and p16 IHC in PSCC clinical outcomes. We searched the PubMed, Embase, and Cochrane databases and identified 34 relevant studies that met our inclusion criteria. Of these, 33 were retrospective cohort studies, and one was a cross-sectional study. Nine studies reported that HPV-positive and p16-positive PSCC had better overall survival (OS) and disease-free survival (DFS). This study highlights the need for a meta-analysis to determine the role of routine HPV status or p16 staining testing as part of the initial diagnosis and staging of PSCC patients worldwide.

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“…Contemporary genetic analysis of 36 patients has demonstrated that p53 alterations within the tumour were associated with LNM independent of p16 status. In patients in whom p16 was negative, p53 mutations had a higher propensity for lymph node metastases [odds ratio (OR) 5.42; 95% confidence interval (95% CI) 1.75-16.80; P ¼ 0.003] [22]. Furthermore, overexpression of antioxidant and tumour suppressor superoxide dismutase (SOD2) and nuclear proliferative protein Ki-67 may also have a role in predicting LNM [23].…”

Section: Predictive Nomogrammentioning

confidence: 99%

Recent developments in the diagnosis and management of N1 penile cancer

O’Brien

McVey

Kelly

et al. 2022

Current Opinion in Urology

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Purpose of review This article presents a critical review of the current literature to provide a brief update on the contemporary advances in diagnosing and managing N1 penile cancer. Recent findings Penile squamous cell carcinoma (pSCC) has evolved from being an orphan field for cancer innovation. Advances in the understanding tumour biology have enabled sophisticated diagnostics and predictive modelling to better characterize inguinal disease. Minimally invasive inguinal lymph node dissection is emerging as a technique that reduces morbidity while maintaining oncological safety. Furthermore, robust clinical trials are underway ,which will provide level one evidence to guide treatment decisions. Exciting advances in the field of immune-oncology offer promise as adjuvant therapies. International collaboration and centralisation of care will be essential to driving translational research and equitable evidence-based care. Summary Improving outcomes for men with pSCC remains a global challenge. Radical inguinal lymph node dissection remains the gold standard for diagnosing and curing N1 disease. Although many promising developments are on the horizon, high-level evidence is required to guide therapy.

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p53 and p16ink4a As Predictive and Prognostic Biomarkers for Nodal metastasis and Survival in A Contemporary Cohort of Penile Squamous Cell Carcinoma

Cited by 14 publications

References 40 publications

p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas with Adverse Prognosis

p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas with Adverse Prognosis

The Prognostic Role of Human Papillomavirus and p16 Status in Penile Squamous Cell Carcinoma—A Systematic Review

Recent developments in the diagnosis and management of N1 penile cancer

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