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Presented by Linda M. Douglas, RDH, BSclinda@farranmedia.com

Innovations in

Saliva-Based Diagnostics

and

Xerostomia Management

Educational Objectives

List the types of biomarker which are found in saliva

Describe how biomarkers for systemic disease are transported into saliva

Describe the oral and systemic conditions associated with a dry mouth

Discuss the value of saliva-based diagnostics in your practice

Create evidence-based clinical care plans and self-care protocols for dry mouth patients.

Liquid Biopsy:Saliva-based Diagnostics for Oral

and Systemic disease

Image courtesy of Dr David Wong

Salivaomics Knowledge Database

Images reproduced with permission from Dr David Wong http://www.hspp.ucla.edu/skb.swf

The UCLA Human Salivary Proteome research project

Salivary Diagnostics

How biomarkers for systemic disease are transported into saliva

Cancer-derived exosome-like microvesiclesare capable of interacting with salivary gland cells

Tumor-derived RNA molecules transported through exosome vesicles from source of tumor, and re-processed into saliva as biomarkers

Wang, X., Kaczor-Urbanowicz, K.E. & Wong, D.T.W. Med Oncol(2017) 34: 7. https://doi.org/10.1007/s12032-016-0863-4

Novel saliva testing Technologies (PCR, OFNASET & EFIRM)

Wei, F, Patel, P, Liao, W, Chaudhry, K, Zhang, L, Arellano-Garcia, M, Hu, S, Elashoff, D, Zhou, H, Shukla, S, Shah, F, Ho, C M, and Wong, D T Electrochemical sensor for multiplex biomarkers detection. Clin Cancer Res, 2009; 15: 4446-4452.

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Types of biomarker which are found in saliva

Metabolomes

Microbiomes

Genomes

Image courtesy of Dr David Wong

Types of biomarker which are found in saliva:Transcriptomes

Messenger RNA

Micro RNA

Current Research on Saliva Testing for

Systemic Diseases Salivary metabolomes aid in

detecting oral SCCC

Salivary microbiome, metabolome & mRNA to detect pancreatic cancer

Zika Test Uses Saliva to Detect Both Nucleic Acids and Antibodies of the Virus

Detecting tumor-causing mutations in saliva

Saliva test Detects Epidermal Growth Factor receptor gene mutations to Dx lung cancer

SaliMark Future Pipeline Products

SaliMark™ LC SaliMark™ SS SaliMark™ D2

Salivary glands may hold key to Parkinson’s diagnosis

Testing submandibular salivary glands to diagnose Parkinson’s disease

Investigating saliva for biomarkers of Parkinson’s disease

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Salivary Biomarkers May Indicate Alzheimer’s Risk

Diagnostic Biomarkers of Alzheimer’s Disease as Identified in Saliva Using 1H NMR-Based Metabolomics, Journal of Alzheimer’s Disease

Saliva Proteins May Aid Early Autism Diagnosis

Consistent with current ideas about autism cause and comorbidities.

January 27 2015 in the journal Autism Research.

Salivary Biomarker linked to Stress, Resilience

Recent research suggests that increased levels of nerve growth

factors in saliva are related to greater resilience and adaptation to

stress .

Attitudes of Dentists, Physicians and Patients towards chairside

screenings

(JADA Jan2010 Vol. 141:1, pp.52-62)

Most DDS sampled would be open to providing medical screenings

Most primary care physicians would welcome screenings and referrals from DDS

Many patients indicated they would regard DDS more highly, if they conducted medical screenings

DNA and Dentistry

≈100 million Americans are infected with periodontal disease. It is recognized to increase risks for diabetes,

heart disease, stroke, and other systemic diseases.Source: http://www.perio.org/resources-products/pdf/48-epidemiology.pdf

Saliva-Based Diagnostics in Your Practice

MyPerioPath

MyPerioID

Alert 2 ™

MyPerioPath ® + MyPerioID ® IL-6

Image courtesy of OralDNA Labs

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Saliva-Based Diagnostics in Your Practice

OraRisk ® HPV OraRisk HSV OraRisk ® Candida OraRisk ® CT/NG OraSure

technologies take-home HIV screening test*

Image courtesy of OralDNA Labs

Celsus One ™ salivary DNA tests

Tests 8 gene markers related to inflammatory response

Image courtesy of OralDNA Labs

Online Ordering and Reporting

Image courtesy of OralDNA Labs

1. Sterile Saline Oral Rinse Sample

3. Ship Overnight

4. Download Report

First DIY test for periodontitis

Tests saliva for matrix aMMP-8, a ‘Destruction Marker’

SaliMark™ OSCC salivary test by PeriRx

Analyzes Salivary Transcriptomes

High sensitivity and specificity

Performed chairside when a suspicious oral lesion is found

• Salivary metabolomes can aid in the detection of oral squamous cell carcinoma. Subjects

with oral squamous cell carcinoma, oral leukoplakia, and those in healthy control groups

demonstrated characteristic salivary metabolic signatures.

DNA Drugmap test

Tests drug metabolism Most FDA-approved

drugs are metabolised by Cytochrome P450 enzyme (CYP450)

Drugmap predicts changes in CYP450 activity.

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Saliva Drug Tests

Saliva MultiDrug Screen test kit ®

QuickScreen ®

iScreen ®

Saliva Glucose test

iQuickIt Saliva Analyzer

Xerostomia—A Growing Problem

Xerostomia affects at least

1 in 10 adults in the general

population

Images courtesy of Dr Andy Wolff

Philip C. Fox, DDS Interactive Textbook on Clinical Symptom Research

'Salivary lubrication, repair, lavage, antimicrobial and buffering properties contribute significantly to the maintenance of the integrity of the hard and soft oral tissue '.

Mandel I D. The role of saliva in maintaining oral homeostasis. J Am Dental Assoc 1989; 119: 298–304

Xerostomia

A 50% reduction in salivary flow occurs before xerostomia is noted .

Ettinger RL. Review: Age Ageing. 1996;25:409-412.Dawes C. Physiologic factors affecting salivary flow rate, oral sugar clearance,

and the sensation of dry mouth in man. J Dent Res. 1987;66(special issue):648-653

Etiology of Salivary Gland Hypofunction

Getting involved in diagnosing xerostomia can provide a window to

your patient’s overall health

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How Diseases & conditions cause Salivary Gland Hypofunction:

Local Factors

Developmental defects Abnormalities of the salivary ducts Tumours Sialoliths (salivary stones) Irradiation of the head and neck Uvulopalatoplasty (removal of uvula)

Jensen SB, Pedersen AM, Reibel J, Nauntofte B. Xerostomia and hypofunction of the salivary glands in cancer therapy. Support Care Cancer. 2003;11:207-225Vissink et al 2003: Oral sequelae of head and neck radiotherapy.

How Diseases & conditions cause Salivary Gland Hypofunction:

Systemic Factors

Dehydration Malnutrition Sympathetic response Damaged nerve supply Inflammatory response due to infection,

or autoimmune disease

Xerogenic Diseases & Conditions

Anxiety Depression Amyloidosis Asthma Lymphoma Menopause

Bulimia nervosa Diabetes insipidus &

diabetes mellitus -cause dehydration

Fibromyalgia

Cherington M. Clinical spectrum of botulism. Muscle Nerve .1998;21:701-710.Blazer T, Latzer Y, Nagler RM. Salivary and gustatory alterations among bulimia nervosa patients.Eur J Clin Nutr. 2007 Jul 11;

Moore PA, et al. Type I diabetes mellitus, xerostomia, and salivary flow rates. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:281-291.

Xerogenic Diseases & Conditions

Dialysis Chronic

Mouthbreathing Cystic fibrosis Hepatitis C

HIV Sarcoidosis Thyroid disease Scleroderma Thalassemia major

Bots CP et al. The management of xerostomia in patients on haemodialysis: Palliative Medicine, Vol. 19, No. 3, 202-207 (2005) Albilia JB et al. Small mouths ... Big problems? A review of scleroderma and its oral health implications. J Can Dent Assoc. 2007 Nov;73(9):831-6. Review. PMID: 18028759

How Drugs cause Salivary Gland Hypofunction

Tissue damage

Altering fluid and electrolyte balance

Effect on neural pathways

Anticholinergic

Sympathomimetic

Vasoconstriction

ADA Council on Scientific AffairsConclusions and

Practice Implications

Health history Comprehensive

evaluation Corrective

actions

Interdisciplinary patient care

Patient education Palliative and

preventive measures

10.14219/jada.2014.44 The Journal of the American Dental Association August 1, 2014 vol. 145 no. 8 867-873

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Risk Assessment: A Xerostomia Screening Questionnaire

1. Does the amount of saliva in your mouth seem too little?

2. Do you have any difficulties swallowing?

3. Does your mouth feel dry when eating a meal?

4. Do you sip liquids to aid in swallowing dry food?

Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomia and objective measures of salivary gland performance. JADA 1987;115(4):581–584

Images reproduced with permission from Professor

Stephen Challacombe

Chronic Salivary Gland Enlargement

Image courtesy of Sjögren’s Syndrome Foundation

Sjögren’s Syndrome Sarcoidosis HIV infection Hepatitis C Bulimia Nervosa Mucoepidermoid Ca Lymphoma

Your text here

Images reproduced with permission from

Eileen McQuade, RDH, BS

Your text here

Other Diagnostic Techniques

Blood testing

Immunologic testing

Biopsy-incisional, or

aspiration cytology

Endoscopy

Diagnostic imaging

Fox PC. Differentiation of dry mouth etiology. AdvDent Res. 1996;10:13-16.

Image reprinted with permission from Medscape

Reference http://emedicine.medscape.com/, 2013,

available at: http://reference.medscape.com/features/slideshow/neck-masses

Hands-On Saliva Testing

Image courtesy of Dr Steven Steinberg

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Saliva-Check BUFFER

Test for Saliva Quality, pH & Buffering Capacity

Image courtesy of http://www.gcamerica.com

Checking Hydration

Image courtesy of http://www.gcamerica.com

Test 1: Unstimulated (resting) saliva

•Collect unstimulated saliva-refrain from swallowing for 30 seconds, then spit into the cup

•Assess colour and consistency of saliva•Test resting salivary pH

Testing pH

Ideal saliva pH 6.8 to 7.5

Images courtesy of http://www.gcamerica.com/

Test 2: Collect Stimulated Saliva-Chew & Spit 5 min

Chew unflavored paraffin wax

Chew and spit saliva into cup every 15-20 seconds for 5 minutes

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The Salivary Flow Index:Salivary Flow Rates

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

Unstimulated Stimulated

0.3 to 0.4mL/min

1 to 2mL/min

<0.1 mL/min

<0.7 mL/min

Normal Abnormal

mL/

min

Assessment of Saliva Saliva: The Movie

Hands-On Saliva Testing

Now Playing“Saliva” by Mew

Test 2 Continued: Testing Stimulated Saliva

Measure volume of Stimulated Saliva collected

Test Stimulated salivary pH

Keep this saliva for Buffer testing

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Test 3: Test Buffering capacity of stimulated saliva

Use pipette to drop saliva onto the three parts of the buffer test pad

Turn pad sideways on a tissue to remove excess saliva

Check the score with the colour chart after two minutes

Buffer Test

Testing capacity to buffer an acid

challenge

Images courtesy of http://www.gcamerica.com/

Testing for Cariogenic Bacteria

Image courtesy of .gcamerica.

Stimulate saliva

Saliva Substitution

Conserve functional salivary gland tissue

Multifaceted Management of Xerostomia and SGH

Prevent Caries, remineralize

Protect soft tissue

Palliation

Hydration

Sjögren’s Syndrome Foundation’s Clinical Practice

Guidelines: Caries Prevention

Fluoride Non-fluoride remineralizing

agents Salivary stimulation Antimicrobials

JADA April 2016,Volume 147, Issue 4, Pages 295–305 Clinical practice guidelines for oral management of Sjögren disease Domenick T. Zero et alwww.sjogren’s.org

Caries Prevention and Remineralization

In-office fluoride varnish Self-applied fluoride

Image courtesy of Oral Science

Image courtesy of 3M Espe

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Calcium and Phosphate Products

Recaldent Tri-Calcium phosphate Nanohydroxyapatite Bioactive glass

(Novamin)

Images courtesy of GC America and 3M ESPE

Silver Diamine Fluoride 38% (SDF)

Arrests caries, even after cavitation

Image courtesy of Oral Science

Xylitol

Stimulates salivation Reduces oral population of Strep

Mutans Reduces acidity & promotes

remineralization Reduces plaque accumulation

Xylitol

Your text here

Images courtesy of Spry, Oral Science, and Carifree

Some Xerostomia Relief Products

All Day spray Basic Bites Biotène BioXtra Colgate Hydris GC Dry

mouth gel Lubricity M I Paste Numoisyn NeutraSal

Optimoist OraMoist Oral 7 SalivaMax Salivasure Saliva Orthana Spry Rain 3M

Theramints™ Xero Lube X-Pur

Quinn et al. Efficacy of a supersaturated calcium p hosphate oral rinse for the prevention and treatment of oral mucositis in patie nts receiving high-dose cancer therapy: a review of current data. Eur J Canc er Care. 22:564-579;2013 .

Supersaturated Calcium phosphate rinse

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Images courtesy of Biotene, AS. Saliva Orthana and Lubricity

MI Paste Plus with Recaldent(CPP/ACP™)

for Xerostomia management

Adds moisture Stimulates salivary

flow Buffers plaque acid Remineralizes Reduces adherence

of Strep. Mutans Relieves sensitivity

Images courtesy of GC America

Initially, this is for the United States only

Clean & Protect

Chlorhexidine

GUM Alcohol-free 0.12% Chlorhexidine Gluconate Oral Rinse

Perio Plus 0.12% Chlorhexidine rinse

PrevoraChlorhexidine VarnishImages courtesy of Oral Dent Pharma, Sunstar

Americas, & Prevora.

Innovative and

Evolving Therapies for Xerostomia

New Research

An artificial salivary gland Calcium and salivary flow Sjögren’s patients have more pro-

inflammatory (IL-17) molecules, and less anti-inflammatory molecules (Del-1)

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Stem cell therapy

Adult Salivary Gland Stem Cells and a Potential Therapy for Xerostomia

Sarah Pringle, Ronald van Os, Robert P Coppes. Regenerative Medicine DOI: 10.1002/stem.1327

Acupuncture

Three points aretreated in each ear:

Shen Men Point Zero Salivary Gland 2

One in the radial aspect of each index finger (Large Intestine 1)Image created by Danielle L. Douglas

Hypnosis

Schiff E, Mogilner JG, Sella E, Doweck I, Hershko O, Ben-Arye E, YaromN. J Pain Symptom Manage. 2009 Jun;37(6):1086-1092.e1. Epub 2009 Jan 31.

Hypnosis for post-radiation xerostomia in head and neck cancer patients: a pilot study

Electronic Stimulation

Saliwell GenNarino

Images courtesy of Dr Andy Wolff

SaliPen

Natural saliva production

Lasting wetness effect

Useful for all dry mouth patients

Images courtesy of Dr Andy Wolff

How to use the SaliPen

No side effects One size fits all Low cost Electro-

stimulation Online orders

Images courtesy of Dr Andy Wolff

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Hyperbaric Oxygen therapy

The Effect of hyperbaric oxygen therapy on quality of life in oral and oropharyngeal cancer patients treated with radiotherapy

Gerlach et al. Int J Oral Maxillofac Surg. 2008; 37(3):255-59

Vaccine for Sjögren's Syndrome

Primary Sjögren's

syndrome and deficiency of

ICA69

The Lancet, Vol 360; Issue 9339, Oct 5th 2002:1063-1069

•Researchers in Toronto assessed the role of the antigen, ICA69 in immunity against Sjogrens syndrome.

Gene therapy

Image created by Danielle L. Douglas

Acquaporin 1 transgenefacilitates formation of water channels in cells

Local use of drugs:Pilocarpine Lollipops

Image courtesy of Eva Grayzel

Quick-Start Guide for Clinicians

Three month recalls Extra-oral exam Intra-oral exam Xerostomia

questionnaire Assess hydration

inside lower lip Test salivary pH

Clinical Oral Dryness Score

In-office fluoride treatments

Desensitization as required

Dietary counseling

Quick-Start Self-Care Guide

Drink water Stimulate saliva

flow * Xylitol gum or

candy Dry mouth spray or

gel as required Avoid exacerbating

factors

High fluoride toothpaste

Calcium & phosphate Petroleum-free lip

balm Omega-3 supplements

1000 mg per day Moist foods low in

acid, salt & sugar

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Thank You!!And now, for theDoor Prize!