# Precision Diagnosis in Cutaneous Head and Neck Squamous Cell Carcinoma

## TL;DR

This review explores how precision diagnostics, including molecular markers and AI, can improve early detection and treatment of cutaneous squamous cell carcinoma.

## Contribution

The paper provides a comprehensive overview of current and emerging precision diagnostic techniques for cSCC.

## Key findings

- Key genetic alterations in cSCC include p53, NOTCH, RAS/MAPK, cell-cycle, and adhesion pathways.
- Optical imaging and AI-based techniques show promise in improving diagnostic accuracy for cSCC.
- Cost and clinical integration remain significant barriers to the widespread adoption of precision diagnostics.

## Abstract

Precision oncology has been evolving rapidly, with increasing emphasis on early detection and personalized diagnostic approaches that translate into tailored treatment algorithms. The integration of molecular markers, quantitative imaging approaches and artificial intelligence (AI) in the diagnostic workflow of cutaneous squamous cell carcinoma (cSCC) has increased accuracy and has the potential to improve early detection rates in these cancers. Sun exposure is the primary etiologic factor in the development of cSCC. The primary objective of this review is to evaluate the current state and future directions of modalities and practices in diagnostic techniques for cSCC. Specifically, this review summarizes the key genetic alterations and potential molecular targets in cSCC. High-risk genetic mutations and pathways implicated in the pathogenesis of cSCC include p53, NOTCH, RAS/MAPK, cell-cycle, and adhesion pathways. This review further explores current and emerging modalities in optical imaging techniques and molecular-based diagnostic modalities in cSCC. Further, we discuss the role of radiomics and AI in the diagnostic work-up of cSCC. These techniques have the potential to enable more accurate risk models that refine conventional histopathology and guide personalized interventions. However, there are limitations to the clinical application of several of these modalities, with cost being an important driver. These challenges have been discussed in detail within this review. Nevertheless, ongoing research is focused on improving the workflow and initiating a shift in clinical practice with application of precision diagnostics as a standard of care.