3 - NCG - INDIA - Rev - Preventive Oncology - Primary - Care
3 - NCG - INDIA - Rev - Preventive Oncology - Primary - Care
3 - NCG - INDIA - Rev - Preventive Oncology - Primary - Care
SUMMARY
RESOURCE-STRATIFIED CLINICAL PRACTICE GUIDELINE SUMMARY
The National Cancer Grid (NCG) formed in 2012 funded by the Government of India through
the Department of Atomic Energy, is amongst the largest cancer networks in the world
formed with the primary mandate of working towards uniform standards of patient care
across India by adopting evidence-based cancer prevention, screening and management
guidelines, which are implementable across the country.
WHO Guidelines for screening of Oral, Breast and Cervical cancers for LMIC settings are
currently available. However, there are challenges for their adoption and implementation due
to large disparities and variations in the availability and access to health care resources.
Recently Government of India have also released broad programmatic guidelines, mainly
focused on opportunistic screening within the existing public health systems framework.
These pose unique challenges such as cost of administration, training of manpower, access to
screening facilities, follow up management and adequate linkages for confirmatory diagnosis
and subsequent treatment. The development of public health care systems varies across
different States in the country as health is a State subject. The health resources allocated
towards cancer control also vary between different States in the country.
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
Hence evidence based screening, diagnosis and management protocols for common
cancers need to be developed to suit different levels of health resource settings. This will
enable identifying the most suitable options for adaptation to the local context.
the largest cancer networks in the world, aims to provide evidence based resource stratified
strategies and approaches that are operationally feasible to help adopt best practices in a
wide range of situations stratified by resources, leveraging with existing health system.
The NCG consensus guidelines and algorithms are consistent with existing evidence and
appropriate in the context of health systems of our country, for a sustainable implementation
of population based cancer screening and early detection program.
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
TABLE 1: Summary of the Resource-Stratified Clinical Practice Guideline for Secondary
Prevention of Cervical Cancer: NCG INDIA
directed Biopsy
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
Visual
assessment for
treatment (VAT) if
colposcopy is not
available.
National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
TABLE 2 : Summary of the Resource-Stratified Clinical Practice Guideline for Secondary
Prevention of Breast Cancer: NCG INDIA
2 Where : Place Health & Wellness Health & Wellness Health & Wellness
for screening Centers Centers Centers (if
Mammography
Primary Health Primary Health facilities are available)
Centers (PHC), Centers (PHC),
Community Health
Community Health Community Health Centers (CHC) (if
Centers (CHC) Centers (CHC) Mammography
facilities are available)
National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
6 Exiting 75 years 75 years of age or 75 years of age or older
Screening older
7 Diagnostic IMAGING 1. Mammography Core biopsy
steps 1. Mammography 2. Ultrasonography
2. Ultrasonography 3. Core biopsy
TISSUE DIAGNOSIS As appropriate (as
CYTOLOGY/PATHO per availability
LOGY of infrastructure and
3. FNAC facilities)
4. Core biopsy
Management of Management of
treatment as per treatment as per Management of
standard standard guidelines. treatment as per
guidelines. standard guidelines.
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
TABLE 2 : Summary of the Resource-Stratified Clinical Practice Guideline for Secondary
Prevention of Oral Cancer: NCG INDIA
5 Target screening All age groups All age groups All age groups
ages 15 years and older 15 years and older
National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
Evaluation by
General Surgeon/
ENT Surgeon
including Dentist at
DH.
9 Diagnostic NEGATIVE: NEGATIVE: NEGATIVE:
Confirmation Follow-up in 12 Follow-up in 12 Follow-up in 12
months months months
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
CERVICAL CANCER SCREENING:
Cervical cancer is the fourth most common cancer affecting women worldwide, after breast,
colorectal, and lung cancers, with 570,000 cases and the fourth leading cause of cancer death
in women with 311,000 deaths in 2018 worldwide. India accounted for 25% of global cervical
cancer mortality burden in 2018. (GLOBOCAN) Cervical cancer incidence rates varied across
population based cancer registries (PBCR) in India with a mean Age Standardised Rate (ASR)
of 22.0 per 100,000.
Considering the evidence generated till date for cervix cancer screening modalities for early
detection of cervical cancers, we present in this document, the current evidence based
recommendations that can be adopted for India for implementing cervical cancer screening
and pre cancer management strategies that will help address the gaps in uniform
implementation at different resource settings in India.
In the past 20 years, large cross sectional studies designed to evaluate the performance of
high-risk human papillomavirus (hrHPV) testing have demonstrated the sensitivity of hrHPV
testing at 66–95%, with specificity between 76% and 95%. HPV test is the most sensitive
among all the screening tests available till date. A large randomized study in India
demonstrated that even a single round of HPV test followed by appropriate management of
the screen positive women could reduce the cervical cancer mortality by 50%. The other
advantages of the test are – the test is objective and highly reproducible, training needs are
not very stringent, point of care tests are now available. The high negative predictive value of
the test can allow prolongation of screening interval up to 10 years in the screen negative
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women.
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
RECOMMENDATIONS: HPV DNA testing as primary screening test has been adopted in many
national programs globally in High and Middle Income resource settings. HPV testing can
replace cytology as a primary screening tool in setups which can afford HPV Screening.
In women who test negative on an HPV test, rescreening should be done after a minimum
interval of five years.
b. Conventional Cytology:
Organised cytology-based cervical screening in the Europe, North America and Australia led
to a substantial reduction of the incidence of cervical cancer in these regions in the past five
decades. Successes of the cytology based screening programs were mainly due to repeated
testing at frequent intervals, high population coverage, and quality-control procedures
adopted in these regions.
The test has several limitations particularly for resource constrained settings – need for highly
skilled cytotechnicians and pathologists, high infrastructural requirements, need for stringent
quality control at each step.
c. Co testing
RECOMMENDATIONS: If resources permit, HPV testing should be the test of first choice.
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
II. CHOICE OF THE SCREENING METHOD: RESOURCE CONSTRAINED SETTING
Visual inspection with acetic acid (VIA) is simple, non invasive and inexpensive visual test,
has easy to learn approach, does not require laboratory involvement, is a real time test with
results available immediately and even non-physicians can be trained to perform the
procedure. The efficiency and cost-effectiveness of Visual inspection with acetic acid
(VIA) has been evaluated in two Randomized Control Trials (RCT) showing a significant
mortality benefit following VIA cervical screening. [35% South India ,31% Mumbai]. The
advantages of VIA are higher sensitivity than cytology, immediate availability of results
allowing management decisions to be taken at the same visit, feasibility of the test being
performed by trained nurses of health workers and low cost. More recently, Sauvaget and
colleagues, after pooling 26 studies from low- and middle income provided summary
estimate of VIA accuracy for sensitivity of 80% (range, 79%–82%), specificity of 92% (range,
91%–92%), PPV of 10% (range, 9%–10%), and NPV of 99%. Effects of factors such as
region, capacity of screener (health worker, nurse, or physician), place of screening, study
period, and size of study population had no effects on VIA accuracy demonstrating the
overall reliability of VIA screening
RECOMMENDATIONS: Visual inspection using acetic acid (VIA) can be adopted as the
screening modality of choice in settings where resources are not adequate to provide HPV
testing.
RECOMMENDATIONS: Twice in a life time Screening between Age of 30 and 49 can be highly
protective and cost-effective which can be considered in Indian context where screening
coverage is extremely low.
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
III. MANAGEMENT & TREATMENT FOR PRE-INVASIVE DISEASE
A screening program will be effective only when there is a mechanism to ensure high
compliance of the screen positive women for further diagnosis and treatment.
RECOMMENDATIONS:
WHO has recommended VIA based Screen and Treat programs for better compliance to
cervical pre cancer treatment especially in regions with poor access to health care facilities.
RECOMMENDATIONS: Primary screening by VIA gives immediate results, which when linked
to cryotherapy facilities to permit a single-visit Screen & Treat strategy. [ Algorithm for
Primary Screening by VIA. CHART 1]
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
IV. SCREENING AND DIAGNOSIS : WHERE AND BY WHOM?
RECOMMENDATIONS:
1. Para Medical workers like ANMs can be trained to perform VIA at Subcentre level and
above.
2. Screen positives should be evaluated for confirmation of the diagnosis at Primary
Health Centers (PHC), Community Health Centers (CHC) and District Hospitals (DH) by
available modalities like cytology, Colposcopy guided biopsy.
3. Biopsies to be performed at PHC, CHC and DH.
4. See and treat approach can be practiced at PHC and above levels.
5. Colposcopy, biopsy and treatment of precancerous lesion at District hospitals.
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
CHART 1 : Cervical Cancer Screening _Primary Screening by VIA & management
of VIA positive Women
Return to routine screening at 3-5 Preferably see & If not, Refer to Skilled
years interval treat Health care provider for
assessment & further
management
Indications of Cryotherapy:
1. Entire lesion visible on
ectocervix Low grade High grade Invasive
2. Lesion not extending to (CIN 1) (CIN 2&3) cancer
endo cervical canal or
vagina
3. No evidence of
suspicious cancer Treatment by Treatment by Refer to tertiary
4. Non Pregnant Cryotherapy LEEP or care centre for
5. No evidence of pelvic PHC/ CHC Conization treatment of
inflammatory disease at DH / SDH Invasive cancer
time of treatment
6. Not menstruating at
time of treatment
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National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
CHART 2: Cervical Cancer Screening _Primary Screening by HPV DNA Test & Management of
women after a positive HPV primary screening test.
Primary Screening
HPV DNA test
National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
CHART 3: Cervical Cancer Screening _ Abnormal Pap Cytology Investigation and Follow Up
Cytology
Normal Positive
National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology & Primary Care
REFERENCES:
12. Sankaranarayanan R, Nene BM, Shastri SS et al. HPV screening for cervical cancer in
rural India.
N Engl J Med 2009; 360: 1385–1394.
13. Ronco G, Giorgi-Rossi P, Carozzi F et al. Results at recruitment from a randomized
controlled trial comparing human papillomavirus testing alone with conventional
cytology as the primary cervical cancer screening test. J Natl Cancer Inst 2008;100:
492 – 501
14. Lawrence von Karsa , Marc Arbyn , Hugo De Vuyst , Joakim Dillner , Lena Dillner ,
Silvia Franceschi et al. European guidelines for quality assurance in cervical
cancer screening. Summary of the supplements on HPV screening and vaccination
Papillomavirus Research 1 (2015) 22–31
15. Tota JE, Bentley J, Blake J, Coutlée F, Duggan MA, Ferenczy A et al. Introduction
of molecular HPV testing as the primary technology in cervical cancer screening:
Acting on evidence to change the current paradigm. Preventive Medicine 98
(2017) 5–14
16. Strategic framework for the Comprehensive Control of Cancer Cervix. ISBN 978-92-
9022-472- 3 World Health Organization, Regional Office for South-East Asia. 2015
17. G. Dijkstra, P. J. F. Snijders, M. Arbyn et al. Cervical cancer screening: on the way to
a shift from cytology to full molecular screening. Annals of Oncology 25: 927–935,
2014
18. Surendra S Shastri, Ketayun Dinshaw, Geetanjali Amin et al. Concurrent evaluation of
visual,
cytological and HPV testing as screening methods for the early detection of cervical
neoplasia in Mumbai, India. Bulletin of the World Health Organization 2005;83:186-
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194.
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24. Denny L, Kuhn L, De Souza M, Pollack AE, Dupree W, Wright TC Jr. Screen-and-treat
approaches for cervical cancer prevention in low-resource settings: a randomized
controlled trial. JAMA. 2005;294:2173–2181.
25. Nene BM, Hiremath PS, Kane S, Fayette JM, Shastri SS, Sankaranarayanan R.
Effectiveness, safety, and acceptability of cryotherapy by midwives for cervical
intraepithelial neoplasia in Maharashtra, India. Int J Gynaecol Obstet. 2008
Dec;103:232-6.
26. Sauvaget C, Muwonge R, Sankaranarayanan R. Meta-analysis of the
effectiveness of cryotherapy in the treatment of cervical intraepithelial neoplasia.
Int J Gynaecol Obstet. 2013 Mar;120:218-23.
27. L Dolman, C Sauvaget, R Muwonge, R Sankaranarayanan. Meta-analysis of the
efficacy of cold coagulation as a treatment method for cervical intraepithelial
neoplasia: A systematic review.. BJOG. 2014 Jul;121(8):929-42
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Breast cancer is the most common cancer and most common cause of cancer related death
among women globally and also in India. An estimated 208,8849 new breast cancer cases
were diagnosed globally in 2018, accounting for 24.2% of all female cancers and the fourth
leading cause of death due to cancers in females with nearly 626,679 women deaths due to
breast cancer. In India the Age Standardised Incidence rate for breast cancer was reported
at 24.7 per 100,000 with 162,468 new cases.
Mammography is the most widely used screening modality, with evidence of benefit for
women aged 40 to 74 years. Clinical breast examination and breast self-exam have also been
evaluated but are of uncertain benefit. Technologies such as ultrasound, magnetic resonance
imaging, tomosynthesis, and molecular breast imaging are being evaluated, usually as
adjuncts to mammography.
Mammography:
Mammography screening has been shown to be associated with a reduction in breast cancer
mortality across a range of study designs, including RCTs and observational studies (trend
analyses, cohort studies, and case-control studies), with most studies demonstrating a
significant benefit. Evidence suggests that mammography screening performed every 12 to
33 months is effective in decreasing breast cancer mortality. Large proportion of the benefit
of screening mammography is maintained by biennial screening.
Screening for breast cancer is associated with false-positive findings leading to recall for
additional imaging or biopsy in women without cancer. The estimates of over diagnosis vary
widely, from less than 5% to more than 50%.
The Canadian National Breast Screening Study- 2, that compared CBE with CBE +
Mammography, did not show any added benefit of adding mammography to CBE. (1,2) The
intermediate analysis of the Trivandrum RCT initiated in 2006 showed early stage detection
of breast cancers with CBE. (3) The Mumbai RCT with CBE, which is one of the largest and
oldest trial with biennial CBE offered four times in one arm versus no screening in the other
arm has shown downstaging with CBE for all age groups (4) and breast cancer mortality
reduction among women more than 50 years. (personal communication, in process of
publishing)
CBE screening in India may be valuable, practical and cost effective option in LMICs. Training
health workers in CBE and using these trained personnel to implement early detection
programmes for breast cancer may provide the only opportunity for women in LMICs to
undergo regular breast examination for early detection of breast cancer.
Breast Self-Examination
Breast self-examination (BSE) has been compared with usual care (no screening activity) and
has not been shown to reduce breast cancer mortality.
Ultrasonography
mammography and clinical examination in the further assessment of both palpable and
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A. Women Aged 50−69 Years: Asymptomatic and at Average Risk For Breast Cancer
B. Women Aged 40−49 Years: Asymptomatic and at Average Risk For Breast Cancer
WHO suggests an organized, population-based screening programme for women aged 40−49
years only if such programme is conducted in the context of rigorous research and monitoring
and evaluation
C. Women Aged 70−75 Years: Asymptomatic and at Average Risk For Breast Cancer
A. Women Aged 50−69 Years: Asymptomatic and at Average Risk For Breast Cancer
B. Women Aged 40−49 Years: Asymptomatic and at Average Risk For Breast Cancer
40−49 years.
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Need to address the value of increasing breast awareness and in improving accessibility for
early clinical diagnosis and prompt treatment in health services
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Positive Criteria:
CBE Negative CBE Positive 1. Change in size and shape of
breast
2. Change in position of nipple
Self Breast Health Awareness & 3. Nipple discharge
Breast Self Examination (BSE) 4. Nipple retraction
5. New Lumps
6. Skin changes (Dimpling of
skin,Peau D’orange)
2.
Clinical Evaluation by Medical Officer at
PHC/ CHC, Surgeon at CHC
Clinical Breast
Examination (CBE) Mammography Mammography
Negative Positive
Screen
CBE Positive every 2 years
1. Nelson HD, Tyne K, Naik A, et al.: Screening for breast cancer: an update for the U.S.
2. Moss SM, Cuckle H, Evans A, et al.: Effect of mammographic screening from age 40
years on breast cancer mortality at 10 years' follow-up: a randomised controlled
trial. Lancet 2006;368,9552:2053-60.
4. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast
cancer screening: an independent review. Lancet.2012;380(9855):1778-1786.
6. Gøtzsche PC, Jørgensen KJ. Screening for breast cancer with mammography.
Cochrane Database Syst Rev. 2013;6:CD001877.
7. Welch HG, Black WC: Overdiagnosis in cancer. J Natl Cancer Inst 2010;102,9:605-13.
10.Final Update Summary: Breast Cancer: Screening. U.S. Preventive Services Task
Force. July
2015.http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummary
Final/brea st-cancer-screening.
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13. Mittra I, Mishra GA, Singh S, Aranke S, Notani P, Badwe R, Miller AB, Daniel EE, Gupta
14. Miller AB, Wall C, Baines CJ, et al.: Twenty five year follow-up for breast cancer
incidence and mortality of the Canadian National Breast Screening Study:
randomised screening trial. BMJ 2014;348:g366.
15. Fenton JJ, Rolnick SJ, Harris EL, et al.: Specificity of clinical breast examination in
community practice. J Gen Intern Med 2007;22,3:332-7.
16. Thomas DB, Gao DL, Ray RM, et al.: Randomized trial of breast self-examination in
Shanghai: final results. J Natl Cancer Inst 2002;94,19:1445-57.
17. Semiglazov VF, Manikhas AG, Moiseenko VM, et al.: [Results of a prospective
randomized investigation [Russia (St.Petersburg)/WHO] to evaluate the significance
of self-examination for the early detection of breast cancer]. Vopr Onkol
2003;49,4:434-41.
18. Teh W, Wilson AR. The role of ultrasound in breast cancer screening. A consensus
statement by the European Group for Breast Cancer Screening. Eur J Cancer.
1998;34,4:449-50.
19. Lord SJ, Lei W, Craft P, et al. A systematic review of the effectiveness of magnetic
resonance imaging (MRI) as an addition to mammography and ultrasound in
screening young women at high risk of breast cancer. Eur J Cancer 2007;43,13:1905-
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17.
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Oral cancer is an important public health problem with increasing incidence and late-stage
presentation. Cancers of the mouth , pharynx and larynx taken together are the seventh most
commonly occurring type of cancer worldwide. India reported Lip, oral cavity cancer at ASIR
of 9.1 for both sexes combine a n d 1 3 . 9 for men. Oral cancer thus accounts as the
highest incidence of malignancy in males and the second highest in females in India.
Smoking, alcohol use, smokeless tobacco use, and HPV infection are the major risk factors for
oral cavity cancer. Smokeless tobacco products and betel quid with or without tobacco are
the major risk factors for oral cavity cancer in India and other neighbouring countries. Human
papillomavirus (HPV) has been shown to be another independent risk factor for oral
squamous cell carcinomas ( OSCC) of the base of the tongue, tonsils, pharynx, and larynx.
Despite the general accessibility of the oral cavity during physical examination, many
malignancies are not diagnosed until late stages of disease. Early detection of oral cancer and
their precursors is the key to reducing the high mortality rate attributable to oral cancer.
The screening tests or diagnostic aids used to improve early detection and diagnosis of oral
precancers and cancers which are available for oral cancer, some of which have been
practiced and studied for many years while others have recently become commercially
available include Oral Visual examination, exfoliative cytology, vital tissue staining (toluidine
blue, Methylene blue), visualization adjuncts (ViziLite Plus with TBlue, ViziLite, Microlux DL,
Orascoptic DK, VELscope), and OralCDx brush biopsy.
A conventional oral visual inspection (0VI) of the oral cavity, using normal (incandescent)
light, has long been the standard method for oral cancer screening. The UK working group on
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screening for oral cancer and precancer in 1990's had concluded that the most suitable
screening for oral cancer and precancer is a thorough and methodical examination in good
lighting of the mucosal surfaces of the oral cavity. A meta-analysis of four studies of OVI
conducted in developing countries using health care auxiliaries as screeners showed an
overall sensitivity of 0.85 (95% CI 0.73, 0.92) and specificity of 0.97 (95% CI 0.93, 0.98)
indicating a satisfactory test performance for an oral examination.
As an alternative Mouth Self Examination (MSE) was evaluated in a study involving 34,766
subjects in India and was found to have low sensitivity of 18% while the specificity was 99.9%.
Overall awareness about oral cancer and its risk factors after introduction of MSE program
was over 80%; but the compliance to seek treatment was reported to be very poor at 32%.
The authors concluded that role of health education in sustained practice of MSE needs to be
evaluated.
Adjunctive Technologies: There is currently no evidence to support the use of like , vital
tissue staining (toluidine blue, Methylene blue), visualization adjuncts (ViziLite Plus with
TBlue, ViziLite, Microlux DL, Orascoptic DK, VELscope), as a screening tool to reduce oral
cancer mortality.
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CONCLUSION
There has been a dramatic increase in the development of tools and devices for oral cancer
screening in the last few decades. However no technology to date has provided definitive
evidence to suggest that it improves the sensitivity or specificity of oral cancer screening
beyond OVI alone. Most studies conducted for these newer devices have been performed
in a setting used to aid in the diagnosis of a lesion that has already been identified by the
naked eye, rather than as true screening tools.
Effective early detection technologies that are easy to perform clinically in primary care
settings combined with an increased public awareness of oral cancer in general will help attain
the goal of decreasing the burden of oral cancer.
DIAGNOSTIC EVALUATION
Oral Brush Cytology: Standard exfoliative oral cytology from the mucosal surface and has
been existence for a long time but has proven unreliable so far.
Oral Brush Biopsy: Brush Biopsy was designed for evaluating clinical lesions that would not
be subjected to standard biopsy due to lack of facilities. Several studies have shown
encouraging results with oral brush cytology for evaluation of oral precancerous lesions. This
may have application in resource challenged areas and could be a risk free method of
evaluating oral lesions.
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CHART : Oral Cancer Screening
Regression No change /
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Progression
National Cancer Grid: Resource Stratified Guidelines_2019/Preventive Oncology
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REFERENCES: ORAL CANCER SCREENING
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16. Mehrotra R, Singh MK, Pandya S, Singh M. The use of an oral brush biopsy without
computer-assisted analysis in the evaluation of oral lesions: A study of 94 patients.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:246-53.
17. Elango KJ, Anandkrishnan N, Suresh A et al. Mouth self-examination to improve oral
cancer awareness and early detection in a high-risk population. Oral
Oncol. 2011;47:620-4.
18. Epstein JB, Güneri P. The adjunctive role of toluidine
blue in detection of oral premalignant and malignant lesions. Curr Opin Otolaryngol
Head Neck Surg. 2009;17:79-87.
19. Chen, Y.W., J.S. Lin, J.H.J. Fong et al. Use of methylene blue as a diagnostic aid in early
detection of oral cancer and precancerous lesions. Br J Oral Maxillofac Surg
2007;45:590-591.
20. Mark W. Lingen, John R. Kalmar, Theodore Karrison et al. Critical Evaluation of
Diagnostic Aids for the Detection of Oral Cancer. Oral Oncol. 2008; 44: 10–22.
21. Brocklehurst P, Kujan O, O'Malley LA et al. Screening programmes for
the early detection and prevention of oral cancer. Cochrane Database Syst Rev. 2013
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