Scope and Objectives

SCOPE: Cervical and oral cancers are the leading causes of deaths in India as per WHO reports 2012. Conventional techniques for cervical and oral cancer detections are limited by specificity and sensitivity, are time-consuming and invasive procedure like the biopsy is necessary. This puts the detection of cancer out of hands for a majority of patients, especially those from rural areas. A technique which is accurate, fast, minimally invasive, and does not depend on skills of the examiner is critical for early diagnosis of cancer. Optical techniques such as fluorescence offer possibilities. In vitro studies with our polarized fluorescence-based probe show that our technique has the potential to detect cervical precancer. This indicates the applicability of the device for in vivo diagnosis in clinics and remote areas. Limitations in conventional techniques in and around Kanpur for oral cancer detection prompted us to test in vivo a device based on fluorescence spectroscopy which shows promise. However, large heterogeneity in lesions within the oral cavity requires a number of measurements. This may be overcome by up-gradation to an imaging tool. Both devices can be further improvised to make them compact fiber optic probes. OBJECTIVES: To deliver compact and cost-effective devices for early detection of cervical and oral precancer. a) In vivo testing of prototypes for detection of cervical and oral precancer. b) Augmenting prototype by wireless control and cost-effective fibre optic probe. c) Up-gradation of oral cancer probe to an imaging device

Deliverables

1. Compact, portable, fast, minimally invasive, automated, user-friendly and biocompatible portable device based on polarized fluorescence for the detection of cervical precancer. 2. Compact, portable, and user-friendly fluorescence-based hand held the device for early detection of oral cancer.
3. An imaging device for detection of oral cancer at an early stage.
4. Smartphone for wireless control of probe via Bluetooth and development of fiber optic probe for both cervical and oral precancer detection.

Scientific Output

1. Preliminary in-vivo analysis on 12 patients has been done. Extraction of intrinsic fluorescence spectra from 12 patients has been done. In the extracted spectra, signatures of major intrinsic fluorophores such as FAD and Porphyrin are seen which are responsible for the changes during the cancer stages. Elimination of these absorption effects is clearly visible in the extracted intrinsic fluorescence spectrum. Till date, 32 patients have been tested. Digital colposcope, which has been recently procured, is being used in the hospital after which pap smear and colposcopic data are used for comparison with spectroscopic data. Collaborating work in AIIMS Bhubaneshwar for cervical precancer detection has been initiated and the system for the testing has been installed in the hospital. Designing of the toolbox for making probe user-friendly is in process. Automation box for the automated motion of the probe is ready.

2. In-vivo detection of oral precancer has been carried out by an in-house developed handheld probe on oral squamous cell carcinoma (OSCC), dysplastic (pre-cancer), and control (normal) groups. In vivo testing on 141 patients have been done. Classification among the groups is continuing by performing principal component analysis (PCA), Mahalanobis distance model, and receiver operating characteristic analysis (ROC). ROC differentiates OSCC to normal, dysplastic to normal and OSCC to dysplastic with sensitivities between 72 % to 98 %, 92 % to 94 %, and 81 % to 93 % and specificities 91 % to 100 %, 86 % to 100 %, and 79 % to 97 % for buccal mucosa, lateral border of tongue and dorsal surface of tongue respectively.

3. In-vivo testing with the modified imaging probe for oral precancer detection is continuing. Till date, 27 patients have been tested. The area around 1cm diameter is imaged through the device which is much larger than the point measurements of spectroscopy. Analysis of 18 cancerous and 9 normal patients showed sensitivity 89% and specificity 100%.

4. Development of Fiber optic probe is continuing. Tabletop experiments for estimation of polarization in an optical fiber has been done.

Results and outcome till date

1. In-vivo testing of prototypes for detection of cervical and oral precancer: - In-vivo testing for cervical precancer detection is continuing with the existing probe. Till date, 32 patients have been tested. Designing of the toolbox for making probe user-friendly is in process. Automation box for the automated motion of the probe is ready. Colposcopy measurements by digital colposcope (procured through the project) have been initiated. For oral precancer detection, in vivo testing using fluorescence spectroscopy is done on 141 patients. To make the system automated and user-friendly, the designed cervical cancer toolbox will be used with due modifications. 2. Augmenting prototype by wireless control and cost-effective fiber optic probe: - Design for Wi-Fi access between spectrometer and smartphone is completed. Design of fibre optic-based system is ready. Experiments for estimation of the state of polarization in optical fiber is continuing. 3. Up-gradation of oral cancer probe to an imaging device: - Design of oral precancer detection probe has been modified to an imaging device. In vivo testing has been initiated. Till date, 27 patients have been tested.

Societal benefit and impact anticipated

Presently in India, the diagnostic tests are available only in Tier I cities. Moreover, these tests are time-consuming. The conventional techniques of diagnosis have a constraint since they require experienced professionals. So the need of the hour is threefold: 1. User friendly and compact diagnostics techniques 2. Accessibility in rural and far-flung areas 3. Robust diagnostic techniques Our technique can meet the above challenges effectively and hence it has the potential of a huge societal impact. Cervical and oral precancer diagnosis with our automated device will be user-friendly making it independent of examiner's subjectivity. Our compact, portable and easy to use device can be made accessible to patients in India's rural areas. The real-time analysis will make the testing faster and hence vital for early diagnosis.

Next steps

1. For cervical cancer probe, interfacing with the spectrometer will be done for the analytic part in the augmented system of automation Pap smear and colposcopy reports of the patients are being awaited from the hospital for comparative studies with our spectroscopic results. 2. Development of App for the automation of the fiber optic probe will be carried out. 3. Designing of the toolbox for making oral cancer detection probe user-friendly will be done. 4. Process for the company set up to aid in the product launch will be initiated. Initial seed money request for the company launching put up as a proposal to the funding agencies

Publications and reports

1. Invivo detection of oral precancer using a fluorescence-based in-house fabricated device: A Mahalanobis distance-based classification is under review with Lasers in medical science journal.

2. Fabrication and invivo detection of oral cancer by fluorescence-based imaging system presented in Photonics 2018 (The international conference on fiber optics and photonics), IIT Delhi, 12-15 Dec 2018.

3. Concentration of FAD has a marker for cervical precancer detection in communication with the Journal of Biophotonics.

Patents

Scholars and Project Staff

1. Partial work of the project is being done by two PhD scholars. 2. One project Engineer has been appointed on regular basis in PI's lab. (Duration: 21 months) 3. Two unskilled workers are continuing.

Challenges faced

1. Delay in receiving histopathology reports from hospitals. 2. Bottlenecks appearing in polarization-based fiber optic probe which have created the delay in one of the objectives.

Other information

1. Applied to the various government agency for funding for the company set up to aid in the product launch. 2. Collaborative work for cervical cancer in vivo testing in AIIMS Bhubaneswar