Journal article

Publication year: 2023

Journal: npj Digital Medicine

Volume number: 6

Issue number: 1

ISSN: 2398-6352

Open access status: Gold

DOI Link: https://doi.org/10.1038/s41746-023-00901-z

Publisher: Nature Research

Abstract: 
Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) represents an OPSCC subgroup with an overall good prognosis with a rising incidence in Western countries. Multiple lines of evidence suggest that HPV-associated tumors are not a homogeneous tumor entity, underlining the need for accurate prognostic biomarkers. In this retrospective, multi-institutional study involving 906 patients from four centers and one database, we developed a deep learning algorithm (OPSCCnet), to analyze standard H & E stains for the calculation of a patient-level score associated with prognosis, comparing it to combined HPV-DNA and p16-status. When comparing OPSCCnet to HPV-status, the algorithm showed a good overall performance with a mean area under the receiver operator curve (AUROC) = 0.83 (95% CI = 0.77-0.9) for the test cohort (n = 639), which could be increased to AUROC = 0.88 by filtering cases using a fixed threshold on the variance of the probability of the HPV-positive class - a potential surrogate marker of HPV-heterogeneity. OPSCCnet could be used as a screening tool, outperforming gold standard HPV testing (OPSCCnet: five-year survival rate: 96% [95% CI = 90-100%]; HPV testing: five-year survival rate: 80% [95% CI = 71-90%]). This could be confirmed using a multivariate analysis of a three-tier threshold (OPSCCnet: high HR = 0.15 [95% CI = 0.05-0.44], intermediate HR = 0.58 [95% CI = 0.34-0.98] p = 0.043, Cox proportional hazards model, n = 211; HPV testing: HR = 0.29 [95% CI = 0.15-0.54] p < 0.001, Cox proportional hazards model, n = 211). Collectively, our findings indicate that by analyzing standard gigapixel hematoxylin and eosin (H & E) histological whole-slide images, OPSCCnet demonstrated superior performance over p16/HPV-DNA testing in various clinical scenarios, particularly in accurately stratifying these patients.

Harvard Citation style: Klein, S., Wuerdemann, N., Demers, I., Kopp, C., Quantius, J., Charpentier, A., et al. (2023) Predicting HPV association using deep learning and regular H&E stains allows granular stratification of oropharyngeal cancer patients, npj Digital Medicine, 6(1), Article 152. https://doi.org/10.1038/s41746-023-00901-z

APA Citation style: Klein, S., Wuerdemann, N., Demers, I., Kopp, C., Quantius, J., Charpentier, A., Tolkach, Y., Brinker, K., Sharma, S., George, J., Hess, J., Stoegbauer, F., Lacko, M., Struijlaart, M., van den Hout, M., Wagner, S., Wittekindt, C., Langer, C., Arens, C., ...Klussmann, J. (2023). Predicting HPV association using deep learning and regular H&E stains allows granular stratification of oropharyngeal cancer patients. npj Digital Medicine. 6(1), Article 152. https://doi.org/10.1038/s41746-023-00901-z