International Society of Urological Pathology (ISUP) Multidisciplinary Consensus on Premalignant and Putative Precursor Lesions of Penile Cancer: Working Group 5 report on Terminology, Grading, and Molecular Testing Practices

Santosh Menon ¹, Diego F Sanchez ², Alcides Chaux ³

¹Department of Pathology, Tata Memorial Centre and Homi Bhabha National Institute, Mumbai, Maharashtra, India.
²Cancer Research UK-Manchester Institute, The University of Manchester.
³Facultad de Medicina, Universidad del Norte, Asuncion, Paraguay.
⁴Indiana University Health and School of Medicine, Indianapolis, IN.
⁵Department of Pathology, The Christie Hospital, Manchester, UK.
⁶Department of Medical Oncology, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.
⁷Diagnostic and Research Institute of Pathology, Medical University Graz, Graz, Austria.
⁸Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL.
⁹Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
¹⁰Department of Surgical Pathology, Aichi Medical University, School of Medicine, Nagakute, Japan.
¹¹MGPO Dermatopathology Associates, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
¹²Institute of Pathology, Bonn, Germany.
¹³Department of Pathology and Laboratory Medicine, Department of Surgery(Urology), Brown University Warren Alpert School, the Legorretta Cancer Center at Brown University, and Brown University Health, Providence, RI.
¹⁴Universidad Nacional de Asuncion, Asuncion, Paraguay.

⁰Department of Pathology, Tata Memorial Centre and Homi Bhabha National Institute, Mumbai, Maharashtra, India.

The American Journal of Surgical Pathology +

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August 19, 2025

View abstract on PubMed

Summary

Pathologists reached consensus on classifying penile intraepithelial neoplasia (PeIN) by HPV status and using p16 IHC, but grading PeIN remains controversial, highlighting a need for standardization.

Area Of Science

Uropathology
Oncology
Molecular Pathology

Background

Penile intraepithelial neoplasia (PeIN) is a precursor to penile squamous cell carcinoma (PSCC), but its classification and diagnosis lack consistency among pathologists.
Current global practices in terminology, grading, and molecular testing for PeIN require assessment and standardization.

Purpose Of The Study

To establish consensus on the classification, grading, and molecular testing of penile intraepithelial neoplasia (PeIN).
To assess current global practices and achieve consensus among international experts on penile cancer precursor lesions.

Main Methods

A preconference survey was distributed to 112 International Society of Urological Pathology (ISUP) members.
Results were presented and consensus was achieved through electronic voting at the ISUP Multidisciplinary Consensus Conference in September 2024.

Main Results

89.4% of respondents classify PeIN based on HPV association; 76% support subtyping.
A majority (82%) voted against grading PeIN, while p16 IHC is widely used (91.5%) for distinguishing HPV-associated PeIN.
p53 IHC and HPV genotyping lack consensus for routine use; reporting of PeIN margins and association with lichen sclerosis is endorsed.

Conclusions

This ISUP consensus paper standardizes PeIN classification, emphasizing HPV-related stratification and p16 IHC staining.
Significant variability persists in PeIN grading and molecular testing, necessitating further research and standardization for improved diagnostic accuracy and clinical relevance.

Keywords:

consensus human papillomavirus penile precursor