Let it shine: Autofluorescence of Papanicolaou-stain improves AI-based cytological oral cancer detection (2407.01869v2)
Abstract: Oral cancer is a global health challenge. It is treatable if detected early, but it is often fatal in late stages. There is a shift from the invasive and time-consuming tissue sampling and histological examination, toward non-invasive brush biopsies and cytological examination. Reliable computer-assisted methods are essential for cost-effective and accurate cytological analysis, but the lack of detailed cell-level annotations impairs model effectiveness. This study aims to improve AI-based oral cancer detection using multimodal imaging and deep fusion. We combine brightfield and fluorescence whole slide microscopy imaging to analyze Papanicolaou-stained liquid-based cytology slides of brush biopsies collected from both healthy and cancer patients. Due to limited cytological annotations, we utilize a weakly supervised deep learning approach using only patient-level labels. We evaluate various multimodal fusion strategies, including early, late, and three recent intermediate fusion methods. Our results show: (i) fluorescence imaging of Papanicolaou-stained samples provides substantial diagnostic information; (ii) multimodal fusion enhances classification and cancer detection accuracy over single-modality methods. Intermediate fusion is the leading method among the studied approaches. Specifically, the Co-Attention Fusion Network (CAFNet) model excels with an F1 score of 83.34% and accuracy of 91.79%, surpassing human performance on the task. Additional tests highlight the need for precise image registration to optimize multimodal analysis benefits. This study advances cytopathology by combining deep learning and multimodal imaging to enhance early, non-invasive detection of oral cancer, improving diagnostic accuracy and streamlining clinical workflows. The developed pipeline is also applicable in other cytological settings. Our codes and dataset are available online for further research.
- The effectiveness of artificial intelligence in detection of oral cancer. International Dental Journal 72, 436–447. doi:10.1016/j.identj.2022.03.001.
- Fluorescence emitted by Papanicolaou-stained urothelial cells improves sensitivity of urinary conventional cytology for detection of urothelial tumors. World Journal of Oncology 11, 204–215. doi:10.14740/wjon1305.
- End-to-end multiple instance learning with gradient accumulation, in: 2022 IEEE International Conference on Big Data (Big Data), IEEE. pp. 2742–2746. doi:10.1109/BigData55660.2022.10020801.
- Multimodal machine learning: A survey and taxonomy. IEEE Transactions on Pattern Analysis and Machine Intelligence 41, 423–443.
- Multi-label classification of multi-modality skin lesion via hyper-connected convolutional neural network. Pattern Recognition 107, 107502.
- Harnessing multimodal data integration to advance precision oncology. Nature Reviews Cancer 22, 114–126.
- A systematic review of artificial intelligence techniques for oral cancer detection. Healthcare Analytics 5, 100304. doi:10.1016/j.health.2024.100304.
- Multiple instance learning: A survey of problem characteristics and applications. Pattern Recognition 77, 329–353. doi:10.1016/j.patcog.2017.10.009.
- Not-so-supervised: A survey of semi-supervised, multi-instance, and transfer learning in medical image analysis. Medical Image Analysis 54, 280–296. doi:10.1016/j.media.2019.03.009.
- Dental hygienists and dentists as providers of brush biopsies for oral mucosa screening. International Journal of Dental Hygiene 21, 524–532. doi:10.1111/idh.12713.
- Global cancer observatory: Cancer today (version 1.1). URL: https://gco.iarc.who.int/today. Lyon, France: International Agency for Research on Cancer. Online; accessed 4 June 2024.
- Learning with privileged information via adversarial discriminative modality distillation. IEEE transactions on pattern analysis and machine intelligence 42, 2581–2593.
- Role of artificial intelligence in the early diagnosis of oral cancer. A scoping review. Cancers (Basel) 13, 4600. doi:10.3390/cancers13184600.
- Characterization of the peri-membrane fluorescence phenomenon allowing the detection of urothelial tumor cells in urine. Cancers 14. doi:10.3390/cancers14092171.
- Early detection of oral potentially malignant disorders: a review on prospective screening methods with regard to global challenges. Journal of Maxillofacial and Oral Surgery 23, 23–32.
- Co-attention fusion network for multimodal skin cancer diagnosis. Pattern Recognition 133, 108990. doi:10.1016/j.patcog.2022.108990.
- Aspergillus in the Papanicolaou stain: morphology, fluorescence and diagnostic feasibility. Cytopathology 9, 381–388. doi:10.1046/j.1365-2303.1998.00123.x.
- A paradigm shift in the prevention and diagnosis of oral squamous cell carcinoma. Journal of Oral Pathology & Medicine 52, 826–833. doi:10.1111/jop.13484.
- Squeeze-and-excitation networks, in: Proceedings of the IEEE conference on computer vision and pattern recognition, pp. 7132–7141.
- Attention-based deep multiple instance learning, in: International conference on machine learning, PMLR. pp. 2127–2136.
- Surveillance, epidemiology, and end results (seer) program. URL: https://seer.cancer.gov. online; accessed 4 June 2024.
- MMTM: Multimodal transfer module for CNN fusion, in: Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR), pp. 13289–13299. doi:10.1109/CVPR42600.2020.01330.
- Digital cytology part 2: artificial intelligence in cytology: a concept paper with review and recommendations from the American Society of Cytopathology Digital Cytology Task Force. Journal of the American Society of Cytopathology 13, 97–110. doi:https://doi.org/10.1016/j.jasc.2023.11.005.
- Deep multiple instance learning versus conventional deep single instance learning for interpretable oral cancer detection. PLOS ONE 19, 1–23. doi:10.1371/journal.pone.0302169.
- The effect of within-bag sampling on end-to-end multiple instance learning, in: 2021 12th International Symposium on Image and Signal Processing and Analysis (ISPA), IEEE. pp. 183–188. doi:10.1109/ISPA52656.2021.9552170.
- The cytologic diagnosis of mycobacterium kansasi tuberculosis by fluorescence microscopy of Papanicolaou-stained specimens. Cytopathology 6, 331–338. doi:10.1111/j.1365-2303.1995.tb00579.x.
- Artificial intelligence in cytopathology: a review of the literature and overview of commercial landscape. Journal of the American Society of Cytopathology 8, 230–241. doi:10.1016/j.jasc.2019.03.003.
- Artificial intelligence for multimodal data integration in oncology. Cancer Cell 40, 1095–1110. doi:10.1016/j.ccell.2022.09.012.
- A deep learning based pipeline for efficient oral cancer screening on whole slide images, in: International Conference on Image Analysis and Recognition, Springer. pp. 249–261. doi:10.1007/978-3-030-50516-5_22.
- A novel multimodal optical imaging system for early detection of oral cancer. Oral and Maxillofacial Pathology 121, 290–300. doi:10.1016/j.oooo.2015.10.020.
- Shape from focus. IEEE Transactions on Pattern analysis and machine intelligence 16, 824–831.
- Multimodal widefield fluorescence imaging with nonlinear optical microscopy workflow for noninvasive oral epithelial neoplasia detection: a preclinical study. Journal of Biomedical Optics 25, 116008. doi:10.1117/1.JBO.25.11.116008.
- Analysis of focus measure operators for shape-from-focus. Pattern Recognition 46, 1415–1432.
- Deep multimodal learning: A survey on recent advances and trends. IEEE signal processing magazine 34, 96–108. doi:10.1109/MSP.2017.2738401.
- Toward a multimodal cell analysis of brush biopsies for the early detection of oral cancer. Cancer Cytopathology 117, 228–235. doi:10.1002/cncy.20028.
- U-Net: Convolutional networks for biomedical image segmentation, in: Medical image computing and computer-assisted intervention–MICCAI 2015: 18th international conference, Munich, Germany, October 5-9, 2015, proceedings, part III 18, Springer. pp. 234–241.
- ImageNet large scale visual recognition challenge. International journal of computer vision 115, 211–252. doi:10.1007/s11263-015-0816-y.
- Comparison of two Papanicolaou staining procedures for automated prescreening. Analytical and Quantitative Cytology 1, 37–42.
- Ex vivo fluorescence imaging of normal and malignant urothelial cells to enhance early diagnosis. Photochemistry and photobiology 83, 1157–1166.
- Clinical study on primary screening of oral cancer and precancerous lesions by oral cytology. Diagnostic Pathology 15, 1–6. doi:10.1186/s13000-020-01027-6.
- The diagnostic accuracy of autofluorescence microscopy of pap smears for oral candidal hyphae. International Journal of Oral & Maxillofacial Pathology 2, 28–34.
- Multimodal artificial intelligence-based pathogenomics improves survival prediction in oral squamous cell carcinoma. Scientific Reports 14. doi:10.1038/s41598-024-56172-5.
- The cytological diagnosis of pneumocystis carinii by fluorescence microscopy of Papanicolaou stained bronchoalveolar lavage specimens. Cytopathology 2, 113–120. doi:10.1111/j.1365-2303.1991.tb00395.x.
- Deep convolutional neural networks for detecting cellular changes due to malignancy, in: Proceedings of the IEEE international conference on computer vision workshops, pp. 82–89.
- Mycobacterial autofluorescence in Papanicolaou-stained lymph node aspirates: A glimmer in the dark? Diagnostic Cytopathology 30, 257 – 260. doi:10.1002/dc.20009.
- Development of an integrated multimodal optical imaging system with real-time image analysis for the evaluation of oral premalignant lesions. Journal of Biomedical Optics 24, 1–10. doi:10.1117/1.JBO.24.2.025003.
- mixup: Beyond empirical risk minimization, in: International Conference on Learning Representations.
- Machine learning for integrating data in biology and medicine: Principles, practice, and opportunities. Information Fusion 50, 71–91. doi:10.1016/j.inffus.2018.09.012.
- Fast computation of mutual information in the frequency domain with applications to global multimodal image alignment. Pattern Recognition Letters 159, 196–203. doi:10.1016/j.patrec.2022.05.022.