Predictive analysis of clinical features for HPV status in oropharynx squamous cell carcinoma: A machine learning approach with explainability

Background and Objective:

Oropharynx Squamous Cell Carcinoma (OPSCC) linked to Human Papillomavirus (HPV) exhibits a more favorable prognosis than other squamous cell carcinomas of the upper aerodigestive tract. Finding reliable non-invasive detection methods of this prognostic entity is key to propose appropriate therapeutic decisions. This study aims to provide a comprehensive method based on pre-treatment clinical data for predicting the patient’s HPV status over a large OPSCC patient cohort and employing explainability techniques to interpret the significance and effects of the features.

Materials and Methods:

We employed the RADCURE dataset clinical information to train six Machine Learning algorithms, evaluating them via cross-validation for grid search hyper-parameter tuning and feature selection as well as a final performance measurement on a 20% sample test set. For explainability, SHAP and LIME were used to identify the most relevant relationships and their effect on the predictive model. Furthermore, additional publicly available datasets were scrutinized to compare outcomes and assess the method’s generalization across diverse feature sets and populations.

Results:

The best model yielded an AUC of 0.85, a sensitivity of 0.83, and a specificity of 0.75 over the testing set. The explainability analysis highlighted the remarkable significance of specific clinical attributes, in particular the oropharynx subsite tumor location and the patient’s smoking history. The contribution of each variable to the prediction was substantiated by creating a 95% confidence intervals of model coefficients by means of a 10,000 sample bootstrap and by analyzing top contributors across the best-performing models.

Conclusions:

The combination of specific clinical factors typically collected for OPSCC patients, such as smoking habits and the tumor oropharynx sub-location, along with the ML models hereby presented, can by themselves provide an informed analysis of the HPV status, and of proper use of data science techniques to explain it. Future work should focus on adding other data modalities such as CT scans to enhance performance and to uncover new relations, thus aiding medical practitioners in diagnosing OPSCC more accurately.