Mobile microscopy as a screening tool for oral cancer in India: A pilot study

RESEARCH ARTICLE Mobile microscopy as a screening tool for oral cancer in India: A pilot study Arunan Skandarajah1, Sumsum P. Sunny2,3, Praveen Gurpur4, Clay D. Reber1, Michael V. D’Ambrosio1, Nisheena Raghavan5, Bonney Lee James3, Ravindra D. Ramanjinappa3, Amritha Suresh2,3, Uma Kandasarma6, Praveen Birur7, Vinay V. Kumar2, HonoriusCezar Galmeanu8, Alexandru Mihail Itu8, Mihai Modiga-Arsu8, Saskia Rausch9, Maria Sramek9, Manohar Kollegal4, Gianluca Paladini10, Moni Kuriakose2,3, Lance Ladic10*, Felix Koch11, Daniel Fletcher1 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Skandarajah A, Sunny SP, Gurpur P, Reber CD, D’Ambrosio MV, Raghavan N, et al. (2017) Mobile microscopy as a screening tool for oral cancer in India: A pilot study. PLoS ONE 12 (11): e0188440. https://doi.org/10.1371/journal. pone.0188440 Editor: Wilbur Lam, Emory University/Georgia Institute of Technology, UNITED STATES Received: March 9, 2017 Accepted: November 7, 2017 Published: November 27, 2017 Copyright: © 2017 Skandarajah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: This study was funded in part by Siemens Healthcare and by USAID through a grant to the UC Berkeley Development Impact Lab, part of USAID’s Higher Education Solutions Network. Siemens contributed to study design, data analysis, preparation of the manuscript, and manuscript publication. 1 Department of Bioengineering, University of California, Berkeley, CA, United States of America, 2 Head and Neck Oncology, Mazumdar Shaw Medical Centre, NH Health city, Bangalore, India, 3 Integrated Head and Neck Oncology Program (DSRG-5), Mazumdar Shaw Center for Translational Research, Mazumdar Shaw Medical Foundation, NH Health City, Bangalore, India, 4 Siemens Healthcare Pvt Ltd, Bangalore, India, 5 Department of Pathology, Mazumdar Shaw Medical Centre, NH Health City, Bangalore, India, 6 Department of Oral and Maxillofacial Pathology, KLE Society’s Institute of Dental Sciences, Bangalore, India, 7 Department of oral medicine and radiology, KLE Society’s Institute of Dental Sciences, Bangalore, India, 8 Siemens S.R.L, Brasov, Romania, 9 Siemens Healthcare GmbH, Erlangen, Germany, 10 Siemens Medical Solutions USA Inc., Princeton, NJ, United States of America, 11 Department of Oral and Maxillofacial Surgery–Plastic Surgery, University of Mainz, Mainz, Germany * Abstract Oral cancer is the most common type of cancer among men in India and other countries in South Asia. Late diagnosis contributes significantly to this mortality, highlighting the need for effective and specific point-of-care diagnostic tools. The same regions with high prevalence of oral cancer have seen extensive growth in mobile phone infrastructure, which enables widespread access to telemedicine services. In this work, we describe the evaluation of an automated tablet-based mobile microscope as an adjunct for telemedicine-based oral cancer screening in India. Brush biopsy, a minimally invasive sampling technique was combined with a simplified staining protocol and a tablet-based mobile microscope to facilitate local collection of digital images and remote evaluation of the images by clinicians. The tablet-based mobile microscope (CellScope device) combines an iPad Mini with collection optics, LED illumination and Bluetooth-controlled motors to scan a slide specimen and capture high-resolution images of stained brush biopsy samples. Researchers at the Mazumdar Shaw Medical Foundation (MSMF) in Bangalore, India used the instrument to collect and send randomly selected images of each slide for telepathology review. Evaluation of the concordance between gold standard histology, conventional microscopy cytology, and remote pathologist review of the images was performed as part of a pilot study of mobile microscopy as a screening tool for oral cancer. Results indicated that the instrument successfully collected images of sufficient quality to enable remote diagnoses that show concordance with existing techniques. Further studies will evaluate the effectiveness of oral cancer screening with mobile microscopy by minimally trained technicians in low-resource settings. Competing interests: Siemens provided partial funding and actively participated in this study. PLOS ONE | https://doi.org/10.1371/journal.pone.0188440 November 27, 2017 1 / 20 Mobile microscopy as a screening tool Some of the Siemens employees are also owners of Siemens shares. Dr. Fletcher is co-founder of CellScope Inc., a company commercializing a cellphone-based microscope. CellScope Inc. had no involvement with the study described in the manuscript. These disclosures do not alter the authors’ adherence to all of the PLOS One policies on sharing data and materials. Introduction Oral cancer, through a convergence of behavioral and infrastructural factors, is the most common type of cancer among men in India and other countries of South Asia [1, 2]. Tobacco and alcohol-related habits predispose individuals to the development of both precancerous lesions and oral cancer [3], and the higher proportion of men with these habits is thought to contribute to the gender differences in oral cancer incidence [2]. Additionally, data from case-control and meta-analytic studies have shown that HPV is also an independent risk factor for the development of oropharyngeal and oral carcinomas [4, 5]. The stage of disease at presentation is a crucial prognostic factor for oral squamous cell carcinoma [6, 7]. While the 5-year survival rate of oral cancer diagnosed at stage I and II is over 80%, in stages III or IV it is less than 40% [6], emphasizing the need for earlier diagnosis of lesions. Definitive diagnosis of oral cancer is achieved by performing biopsy followed by histological examination of suspicious lesions [8–10]. This method involves examination of the oral cavity and the use of either a scalpel or a punch biopsy and histopathologic processing followed by a specialist’s interpretation. The sample collection is invasive and painful, however, improper sample handling and transfer to a histology facility can preclude its use for providing a diagnosis [11]. As a result, biopsies are normally performed in a hospital setting or under the direction of a skilled clinician. The first point of contact for the majority of patients seeking care, particularly in a rural setting, is not a centralized facility that can provide these types of services. A visual examination for suspicious lesions is the standard screening approach for referring patients from a primary care setting to a centralized location for biopsy and care [7, 12, 13], but its specificity for precancerous lesions is low. This in turn reduces the likelihood (...truncated)