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

112 pathologists surveyed on how to classify penile precancer; 82% ultimately voted to abandon grading after starting nearly split 51/49

Journal: American Journal of Surgical Pathology | Published: 2025-08-20 | Type: Consensus Statement / Practice Guideline | PMID: 40826809 Authors: Menon S et al. — multinational panel spanning Tata Memorial Centre (Mumbai), University of Manchester, MD Anderson Cancer Center, Moffitt Cancer Center, Indiana University, Medical University Graz, and Aichi Medical University Funding/COI: Funding not listed. Authors disclose no financial conflicts of interest.

Summary

Penile intraepithelial neoplasia (PeIN) — the main precursor lesion to penile squamous cell carcinoma — has no standardized classification system, leaving pathologists diagnosing it inconsistently worldwide. The International Society of Urological Pathology (ISUP) ran a pre-conference survey of 112 pathologists, then convened a multidisciplinary consensus meeting in September 2024 to hash out terminology, grading, and which biomarkers to use. The headline result: grade PeIN no more — 82% voted against grading it at the conference, a striking reversal from the pre-conference split where just over half initially favored grading.

Claims

• 89.4% of the 112 surveyed pathologists classify PeIN based on HPV association
• 76% support subtyping into basaloid and warty (HPV-associated) plus differentiated (HPV-independent) subtypes
• Pre-deliberation: 51.3% favored grading PeIN; post-conference voting: 82% voted against grading
• p16 immunohistochemistry (IHC) is used by 91.5% of respondents to distinguish HPV-associated from HPV-independent PeIN — endorsed as standard practice
• p53 IHC and HPV genotyping did not achieve consensus for routine clinical use
• Reporting PeIN margins and its association with lichen sclerosis were widely endorsed practices

Study Quality

This is a consensus paper, not a clinical study, so standard quality metrics don't apply cleanly. The methodology follows a defensible two-step model: survey to map current practice variation, then a structured conference with electronic voting to drive convergence. The sample of 112 ISUP members — predominantly genitourinary pathology specialists — is reasonable for expert consensus work, though it is a convenience sample drawn from a self-selected slice of ISUP's membership.

The pre/post voting design warrants scrutiny. A 30-point swing on grading (51% for → 82% against) shows how substantially conference deliberation reshaped the "consensus." That is not inherently a flaw — deliberation is the mechanism — but it means the published position reflects what expert opinion converged to under a specific framing at a specific moment in 2024, not a stable pre-existing agreement. Who made the most persuasive arguments in that room matters, and that is not recoverable from the paper.

Red Flags

• 112 respondents from an international society with far larger membership — heavy self-selection toward pathologists already engaged with this classification debate
• "Predominantly genitourinary specialists" almost certainly overrepresents expert opinion and underrepresents how community pathologists handle PeIN in routine practice
• Funding source not disclosed; unclear whether conference costs were borne by ISUP, the journal, or industry
• The dramatic pre/post swing on grading raises questions about whose arguments carried the room — the paper cannot answer that
• Subtyping of HPV-independent PeIN remains unresolved; the consensus explicitly flags this as an open area, limiting immediate utility for that subset

Strengths

• Multinational, multidisciplinary panel (pathology, oncology, surgery) from major cancer centers across four continents
• Two-stage process generates more durable consensus than solo expert opinion
• Clear, actionable outputs: HPV-based classification endorsed, p16 IHC codified as standard, grading abandoned
• No financial conflicts of interest declared
• Honest about residual uncertainty rather than projecting false agreement where none exists

Verdict

If you work in genitourinary pathology or treat penile cancer, this paper matters: it settles two standing debates (use HPV classification; stop grading PeIN) and locks in p16 IHC as the diagnostic standard. For a broader audience, it is a window into how clinical consensus is actually manufactured — structured deliberation among selected experts converting a near-coin-flip into an 82% supermajority in one conference. The methodology is solid for what it is. The open questions it leaves — particularly around HPV-independent PeIN subtyping — are the more interesting scientific problems, and this paper does not resolve them.