# CLEAR-HPV: Interpretable concept discovery for human-papillomavirus-associated morphology in whole-slide histology

arXiv: https://arxiv.org/abs/2602.05126 · HTML: https://mlsanity.com/paper/2602.05126/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 14 of its 52 references that are in the map.
- First posted on arXiv 4 Feb 2026.

## Builds on (most cited first, 14 of 14)

- [Emerging Properties in Self-Supervised Vision Transformers](https://mlsanity.com/paper/2104.14294/) (2021)
- [Grad-CAM: Visual Explanations from Deep Networks via Gradient-based Localization](https://mlsanity.com/paper/1610.02391/) (2016)
- [Explainable Artificial Intelligence (XAI): Concepts, Taxonomies, Opportunities and Challenges toward Responsible AI](https://mlsanity.com/paper/1910.10045/) (2019)
- [Concept Bottleneck Models](https://mlsanity.com/paper/2007.04612/) (2020)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [A Survey on Explainable Artificial Intelligence (XAI): Towards Medical XAI](https://mlsanity.com/paper/1907.07374/) (2019)
- [Explainable Artificial Intelligence: Understanding, Visualizing and Interpreting Deep Learning Models](https://mlsanity.com/paper/1708.08296/) (2017)
- [Self supervised contrastive learning for digital histopathology](https://mlsanity.com/paper/2011.13971/) (2020)
- [Explaining Classifiers with Causal Concept Effect (CaCE)](https://mlsanity.com/paper/1907.07165/) (2019)
- [Transferable Visual Words: Exploiting the Semantics of Anatomical Patterns for Self-supervised Learning](https://mlsanity.com/paper/2102.10680/) (2021)
- [HGCLIP: Exploring Vision-Language Models with Graph Representations for Hierarchical Understanding](https://mlsanity.com/paper/2311.14064/) (2023)
- [RadAlign: Advancing Radiology Report Generation with Vision-Language Concept Alignment](https://mlsanity.com/paper/2501.07525/) (2025)
- [Probabilistic Conceptual Explainers: Trustworthy Conceptual Explanations for Vision Foundation Models](https://mlsanity.com/paper/2406.12649/) (2024)

## Abstract (arXiv)

Human papillomavirus (HPV) status is a critical determinant of prognosis and treatment response in head and neck and cervical cancers. Although attention-based multiple instance learning (MIL) achieves strong slide-level prediction for HPV-related whole-slide histopathology, it provides limited morphologic interpretability. To address this limitation, we introduce Concept-Level Explainable Attention-guided Representation for HPV (CLEAR-HPV), a framework that restructures the MIL latent space using attention to enable concept discovery without requiring concept labels during training. Operating in an attention-weighted latent space, CLEAR-HPV automatically discovers keratinizing, basaloid, and stromal morphologic concepts, generates spatial concept maps, and represents each slide using a compact concept-fraction vector. CLEAR-HPV's concept-fraction vectors preserve the predictive information of the original MIL embeddings while reducing the high-dimensional feature space (e.g., 1536 dimensions) to only 10 interpretable concepts. CLEAR-HPV generalizes consistently across TCGA-HNSCC, TCGA-CESC, and CPTAC-HNSCC, providing compact, concept-level interpretability through a general, backbone-agnostic framework for attention-based MIL models of whole-slide histopathology.