The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs—Part A: Renal, Penile, and Testicular Tumours

Moch, Holger; Amin, Mahul B.; Berney, Daniel M.; Compérat, Eva; Gill, Anthony J.; Hartmann, Arndt; Menon, Santosh; Raspollini, Maria Rosaria; Rubin, Mark A.; Srigley, John R.; Tan, Puay Hoon; Tickoo, Satish K.; Tsuzuki, Toyonori; Turajlic, Samra; Cree, Ian A.; Netto, George J.

doi:10.1016/j.eururo.2022.06.016

Cited by 320 publications

(282 citation statements)

References 71 publications

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“…The same kit was used for HPV genotyping. This system allows the genotyping of HPV 16,18,31,33,35,39,45,51,52,56,58,59,68,26,53,66,70,73,82,6,11,40,42,43,44,54,61,62,67,81, 83 and 89. HPV DNA-positive samples not hybridizing with any of the 32 probes were classified as HPV type X (HPV X or undetermined type).Each run was performed with positive and negative controls to monitor the efficiency of DNA isolation, PCR amplification, hybridization, and genotyping procedures.…”

Section: Tissue Preparation Nucleic-acid Isolation and Hpv-dna Detectionmentioning

confidence: 99%

“…Several risk factors for PSCC have been identified, including sexual behavior, history of warts/condylomas/human papillomavirus (HPV) infection, lack of circumcision, phimosis, poor penile hygiene, smoking and chronic inflammatory conditions such as lichen sclerosus [ 3 ]. In its 2016 classification, the World Health Organization (WHO) recommended separating PSCC based on their HPV status into HPV-associated and HPV-independent tumors [ 4 , 5 ], with this categorization having been maintained in the recent WHO 2022 revision [ 6 ]. This WHO classification recognizes a clear association between histological types and their relationship with HPV, with several histological variants of PSCC that are typically HPV-associated and other histological variants known as HPV-independent [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…In its 2016 classification, the World Health Organization (WHO) recommended separating PSCC based on their HPV status into HPV-associated and HPV-independent tumors [ 4 , 5 ], with this categorization having been maintained in the recent WHO 2022 revision [ 6 ]. This WHO classification recognizes a clear association between histological types and their relationship with HPV, with several histological variants of PSCC that are typically HPV-associated and other histological variants known as HPV-independent [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Penile Squamous Cell Carcinomas in Sub-Saharan Africa and Europe: Differential Etiopathogenesis

Manzotti

Chulo

Campo

et al. 2022

Cancers

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Penile squamous cell carcinomas (PSCC) are classified by the World Health Organization into two categories based on their relationship with the human papillomavirus (HPV): HPV-associated and HPV-independent. We compared a cohort of PSCC from Mozambique, a sub-Saharan country in southeast Africa with a high prevalence of HPV and HIV infection, and Spain, a country in southwestern Europe with a low prevalence of HPV and HIV, to study the distribution of the etiopathogenic categories of these tumors in both sites. A total of 79 PSCC were included in the study (28 from Mozambique and 51 from Spain). All cases underwent HPV-DNA polymerase chain reaction (PCR) testing, genotyping, and immunohistochemistry for p16 and p53. Any PSCC showing either p16 overexpression or HPV-DNA in PCR analysis was considered HPV-associated. Overall, 40/79 (50.6%) tumors were classified as HPV-associated and 39 (49.4%) as HPV-independent. The two sites showed marked differences: 25/28 (89.3%) tumors from Mozambique and only 15/51 (29.4%) from Spain were HPV-associated (p < 0.001). HPV16 was the most frequent HPV type identified in 64.0% (16/25) of the HPV-associated tumors from Mozambique, and 60.0% (9/15) from Spain (p = 0.8). On average, patients from Mozambique were almost two decades younger than those from Spain (mean age 50.9 ± 14.9 and 69.2 ± 13.3, respectively [p < 0.001]). In conclusion, significant etiopathogenic differences between PSCC in Mozambique and Spain were observed, with a remarkably high prevalence of HPV-associated tumors in Mozambique and a relatively low prevalence in Spain. These data may have important consequences for primary prevention of PSCC worldwide.

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Section: Tissue Preparation Nucleic-acid Isolation and Hpv-dna Detectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Penile Squamous Cell Carcinomas in Sub-Saharan Africa and Europe: Differential Etiopathogenesis

Manzotti

Chulo

Campo

et al. 2022

Cancers

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“…18 Departments of Clinical Pharmacology, Pharmacy and Biochemistry, University of Tuebingen, Tuebingen, Germany. 19 Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year…”

Section: Supplementary Informationmentioning

confidence: 99%

“…Proposed already two decades ago, the 2016 WHO classification of renal cancer distinguished between pRCC type 1 and type 2 [ 5 ]. Notably, based on recent molecular studies suggesting that pRCC type 2 may not constitute a single well-defined entity, pRCC subclassification into type 1 and type 2 is no longer recommended in the updated 2022 WHO classification [ 17 , 19 ]. Our approach distinguishes pure subtypes from molecularly mixed ones with features from different subtypes, thus enabling the detection of a new class of high-risk tumors with intermediate subtypes.…”

Section: Introductionmentioning

confidence: 99%

A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy

Büttner

Winter

Stühler³

et al. 2022

Genome Med

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Background Renal cell carcinoma (RCC) is a heterogeneous disease comprising histologically defined subtypes. For therapy selection, precise subtype identification and individualized prognosis are mandatory, but currently limited. Our aim was to refine subtyping and outcome prediction across main subtypes, assuming that a tumor is composed of molecular features present in distinct pathological subtypes. Methods Individual RCC samples were modeled as linear combination of the main subtypes (clear cell (ccRCC), papillary (pRCC), chromophobe (chRCC)) using computational gene expression deconvolution. The new molecular subtyping was compared with histological classification of RCC using the Cancer Genome Atlas (TCGA) cohort ( n = 864; ccRCC: 512; pRCC: 287; chRCC: 65) as well as 92 independent histopathologically well-characterized RCC. Predicted continuous subtypes were correlated to cancer-specific survival (CSS) in the TCGA cohort and validated in 242 independent RCC. Association with treatment-related progression-free survival (PFS) was studied in the JAVELIN Renal 101 ( n = 726) and IMmotion151 trials ( n = 823). CSS and PFS were analyzed using the Kaplan–Meier and Cox regression analysis. Results One hundred seventy-four signature genes enabled reference-free molecular classification of individual RCC. We unambiguously assign tumors to either ccRCC, pRCC, or chRCC and uncover molecularly heterogeneous tumors (e.g., with ccRCC and pRCC features), which are at risk of worse outcome. Assigned proportions of molecular subtype-features significantly correlated with CSS (ccRCC ( P = 4.1E − 10), pRCC ( P = 6.5E − 10), chRCC ( P = 8.6E − 06)) in TCGA. Translation into a numerical RCC-R(isk) score enabled prognosis in TCGA ( P = 9.5E − 11). Survival modeling based on the RCC-R score compared to pathological categories was significantly improved ( P = 3.6E − 11). The RCC-R score was validated in univariate ( P = 3.2E − 05; HR = 3.02, 95% CI: 1.8–5.08) and multivariate analyses including clinicopathological factors ( P = 0.018; HR = 2.14, 95% CI: 1.14–4.04). Heterogeneous PD-L1-positive RCC determined by molecular subtyping showed increased PFS with checkpoint inhibition versus sunitinib in the JAVELIN Renal 101 ( P = 3.3E − 04; HR = 0.52, 95% CI: 0.36 − 0.75) and IMmotion151 trials ( P = 0.047; HR = 0.69, 95% CI: 0.48 − 1). The prediction of PFS significantly benefits from classification into heterogeneous and unambiguous subtypes in both cohorts ( P = 0.013 and P = 0.032). Conclusion Switching from categorical to continuous subtype classification ...

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Renal Cell Carcinoma

Rose,

Kim

2024

JAMA

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ImportanceRenal cell carcinoma (RCC) is a common malignancy, with an estimated 434 840 incident cases worldwide in 2022. In the US, it is the sixth most common cancer among males and ninth among females.ObservationsClear cell RCC is the most common histologic subtype (75%-80% of cases) and is characterized by inactivation of the von Hippel Lindau (VHL) tumor suppressor gene. Many patients (37%-61%) are diagnosed with RCC incidentally on an abdominal imaging study such as ultrasound or computed tomographic scan, and 70% of patients have stage I RCC at diagnosis. Although its incidence has increased approximately 1% per year from 2015 through 2019, the mortality rate of RCC has declined about 2% per year in the US from 2016 through 2020. Patients with a solid renal mass or complex cystic renal mass should be referred to urology. Treatment options for RCC confined to the kidney include surgical resection with partial or radical nephrectomy, ablative techniques (eg, cryoablation, radiofrequency ablation, radiation), or active surveillance for some patients (especially those with renal masses &lt;2 cm). For patients with renal masses less than 4 cm in size (48% of patients), partial nephrectomy can result in a 5-year cancer-specific survival of more than 94%. For advanced or metastatic RCC, combinations of immune checkpoint inhibitors or the combination of immune checkpoint inhibitors with tyrosine kinase inhibitors are associated with tumor response of 42% to 71%, with a median overall survival of 46 to 56 months.Conclusions and RelevanceRCC is a common malignancy that is often diagnosed incidentally on an abdominal imaging study. Seventy percent of patients are diagnosed with stage I RCC and 11% of patients with stage IV. First-line treatments for early-stage RCC are partial or radical nephrectomy, which can result in 5-year cancer-specific survival of more than 94%, ablative techniques, or active surveillance. New treatment options for patients with metastatic RCC include immune checkpoint inhibitors and tyrosine kinase inhibitors.

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The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs—Part A: Renal, Penile, and Testicular Tumours

Cited by 320 publications

References 71 publications

Penile Squamous Cell Carcinomas in Sub-Saharan Africa and Europe: Differential Etiopathogenesis

Penile Squamous Cell Carcinomas in Sub-Saharan Africa and Europe: Differential Etiopathogenesis

A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy

Renal Cell Carcinoma

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