Deep multiple instance learning versus conventional deep single instance learning for interpretable oral cancer detection

PLoS One. 2024 Apr 30;19(4):e0302169. doi: 10.1371/journal.pone.0302169. eCollection 2024.

Abstract

The current medical standard for setting an oral cancer (OC) diagnosis is histological examination of a tissue sample taken from the oral cavity. This process is time-consuming and more invasive than an alternative approach of acquiring a brush sample followed by cytological analysis. Using a microscope, skilled cytotechnologists are able to detect changes due to malignancy; however, introducing this approach into clinical routine is associated with challenges such as a lack of resources and experts. To design a trustworthy OC detection system that can assist cytotechnologists, we are interested in deep learning based methods that can reliably detect cancer, given only per-patient labels (thereby minimizing annotation bias), and also provide information regarding which cells are most relevant for the diagnosis (thereby enabling supervision and understanding). In this study, we perform a comparison of two approaches suitable for OC detection and interpretation: (i) conventional single instance learning (SIL) approach and (ii) a modern multiple instance learning (MIL) method. To facilitate systematic evaluation of the considered approaches, we, in addition to a real OC dataset with patient-level ground truth annotations, also introduce a synthetic dataset-PAP-QMNIST. This dataset shares several properties of OC data, such as image size and large and varied number of instances per bag, and may therefore act as a proxy model of a real OC dataset, while, in contrast to OC data, it offers reliable per-instance ground truth, as defined by design. PAP-QMNIST has the additional advantage of being visually interpretable for non-experts, which simplifies analysis of the behavior of methods. For both OC and PAP-QMNIST data, we evaluate performance of the methods utilizing three different neural network architectures. Our study indicates, somewhat surprisingly, that on both synthetic and real data, the performance of the SIL approach is better or equal to the performance of the MIL approach. Visual examination by cytotechnologist indicates that the methods manage to identify cells which deviate from normality, including malignant cells as well as those suspicious for dysplasia. We share the code as open source.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comparative Study

MeSH terms

  • Deep Learning*
  • Humans
  • Mouth Neoplasms* / diagnosis
  • Mouth Neoplasms* / pathology
  • Neural Networks, Computer

Grants and funding

This work is supported by: Sweden’s Innovation Agency (VINNOVA) https://www.vinnova.se/en/apply-for-funding/funded-projects/, grants 2017-02447, (J.L.), 2021-01420 (J.L.), and 2020-03611 (J.L.), the Swedish Research Council https://www.vr.se/english/swecris.html#/, grant 2017-04385 (J.L.) and 2022-03580_VR (N.S.), and Cancerfonden https://www.cancerfonden.se/forskning, project number 22 2353 Pj (J.L.) and project number 22 2357 Pj (N.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.