Lab Medicine Rounds | Challenges of Saliva Testing

In this episode of “Lab Medicine Rounds,” Justin Kreuter, M.D., sits down with Darci Block, Ph.D., assistant professor of Laboratory Medicine and Pathology and consultant in Clinical Core Laboratory Services at Mayo Clinic, to discuss challenges of saliva testing.

Show Notes

Timestamps:

0:00 Intro

00:53 Why is the medical field interested in saliva?

02:00 What sorts of information could be gleaned from saliva?

03:17 Are there certain limitations of what could come out of saliva testing?

04:56 Can you elaborate what you mean when you say “matrix?”

06:16 How do you approach navigating what could be interferences?

08:16 Would that be considered part of the matrix? Or is the matrix just the specimen itself?

9:29 Could you elaborate those preanalytic variables a clinician may have top of mind, or what might be in their sphere of control, influence, awareness?

11:41 What’s your advice to laboratory professionals about how we can detect when these kinds of things are going awry, or how do you keep your finger on the pulse of how your colleagues on the clinical side are using your tests?

13:34 What do you see as the future for saliva testing like?

14:54 Outro

Resources:

https://www.aacc.org/cln/articles/2022/janfeb/saliva-in-the-spotlight

https://news.mayocliniclabs.com/2022/04/07/darci-block-ph-d-discusses-saliva-testing-in-aaccs-clinical-laboratory-news/

What is Lab Medicine Rounds?

A Mayo Clinic podcast for laboratory professionals, physicians, and students, hosted by Justin Kreuter, M.D., assistant professor of laboratory medicine and pathology at Mayo Clinic, featuring educational topics and insightful takeaways to apply in your practice.

- This is lab medicine
rounds, a curated podcast

for physicians, laboratory
professionals and students.

I'm your host, Justin Kreuter,
the bow tie, bandit of blood

a transfusion medicine
pathologist at Mayo clinic.

And today we're rounding
with Dr. Darci Block,

an assistant professor
of laboratory medicine,

pathology, and consultant in clinical core

laboratory services here
at Mayo clinic to talk

about the challenges of saliva testing.

So thanks for joining us today Dr. Block.

- Yeah. Thank you, Dr. Kreuter
for having me, I'm excited

to be featured on this podcast,
'cause I haven't been yet.

- Well, Hey, we came across an article

of you talking about or where
you were interviewed talking

about saliva testing and we
said, how can we fast this up?

So I'm kind of curious why is

the medical field interested in saliva?

- So I can only really speculate.

I'm actually not an expert
of saliva testing at all

but I think that the interest really grew

maybe exploded during
the COVID pandemic when

there was a major lockdown but yet

this desire to be able to test,
either as a population or,

so you can see if it's safe
to go visit your grandma

to be able to have access to testing

for COVID during the pandemic
and now moving forward.

And I think it just
represented an easier way

so that we could avoid so
many nasopharyngeal swabs

and other more, those invasive type tests

that require, a medical person to collect.

- Yeah, I feel you on
that. My youngest daughter

is really quite nasal swab
adverse, as probably most of us.

So that ease of testing
that really kind of

is a theme that we see in laboratory

medicine or at least it seems like it.

What sorts of information
could be gleaned from saliva?

- Yeah. So I think, I think
the medical community thought

of saliva because it's not
a new matrix for testing.

So we know that it's useful or can be used

in a variety of different settings.

So salivary cortisol is
kind of that primary example

we think of in chemistry, as

because it's a sample
that needs to be collected

at a particular time of the day.

That's not really amenable to being

at the laboratory, it's kind
of a midnight collection.

So if you can tell a patient to,

set your alarm and spit in
a tube and send it to us,

and we get the answer we need,
it makes it more convenient.

So I think the convenience
aspect has been around,

also featured in that article,

you referenced where some
other researchers who,

are looking at being able to try

and screen populations for things like,

upper GI face, head, neck, cancers.

And so, again, trying to do a lot

of testing at a population
level, they're looking

at saliva is, really
helping to accomplish that.

- I hadn't thought about that.

I mean, I get you on the ease of use

but I had forgotten
about kind of the timing

and how that also kind of plays

into getting the sample, when you need it.

I'm kinda curious. I mean, just on the,

at the 10,000 foot view, are
there certain limitations

of what could come out of saliva testing?

- Yeah. So it's not going to be perfect

for any test and probably
very few tests in actuality

really because, saliva is kind of...

to really over oversimplify
the composition of it

it represents sort of an ultra filtrate,

of what might be circulating in blood.

So for example, the
cortisol will show up there

but the sensitivity of
our methods are such

that we're, they're designed to measure

analyte concentrations
that you would see in blood

but they may be at much
lower concentrations

in saliva and therefore be undetectable.

So that's a problem. The reason I think

they reached out to me to talk about

this topic was when it
comes to testing saliva on

as an alternate specimen
type, we have to think

about things like matrix interferences.

Actually one of the biggest challenges

is actually in the collection itself.

So, if you just give someone a tube

and say, "Spit", there's a lot

of different things that come into play,

what did they use to clean
their teeth with that morning?

Could that interfere with the testing?

Some of the tests have a
larger volume requirement.

So to say, and so, there's some protocols

where you actually give them like

a little sucker that has, citric acid

or something kind of sour
to induce saliva flow.

And so then you have to think about, well

does the different components or foams,

or different things that we use

that could potentially
interfere with testing.

So it's very nuanced, I would say.

- Oh, interesting. Yeah, so we've got

students that are
listeners of this podcasts.

I wonder if you could
just kind of elaborate

what you mean when you say matrix.

- So really that composition of the sample

if you think about blood, it has

a lot of protein, a lot of different types

of factors, coagulation
factors, small analytes,

big analytes at a whole
spectrum of concentrations.

And so when we even just pipette a sample

there's a viscosity difference between,

something like water or
serum, versus even just

whole blood or some of the sticky

gooey things that come out
of other places of the body.

So we have to just keep in mind

that the composition of it
could potentially interfere

or its actual physical
properties could make it,

less amenable to being able to go

through that testing process,
the pipetting et cetera.

- And given you were talking about

the different possibilities
for interference,

like the idea of, maybe the type

of toothpaste that I might use.

I mean, I don't know, interestingly enough

as you said that I was thinking,

nowadays it seems like the, the charcoal

in the toothpaste is something that I see

when I go and get toothpaste
for myself and my family.

And, and I mean, charcoal
has been long known

as a substance that can,
absorb certain things

out of our, it can absorb certain things.

And so I'm curious, how does one...

as somebody who runs
saliva testing in their lab

how do you approach navigating
what could be interferences?

'Cause as you're saying, right,

we always wanna be giving
accurate test results

to our clinicians or as accurate
as, catching these things

that may be interfering
with the ultimate result.

- Yeah. So we, this is not
unique to my laboratory.

All of our laboratories
have to demonstrate accuracy

precision, et cetera, for the
tests, even tests that are

meant to be used for that sample type.

So for the example of
blood or a urine sample

we have to verify that the test
actually performs correctly.

So when we change the
specimen type, such as

testing saliva, we have to verify.

And usually we do that
by, some accuracy studies

things like spiking in a known amount

of the analyte and being
able to demonstrate

that we recover that
concentration back out

that there isn't something
that's, either sponging it up

or causing a falsely
elevated signal, for example.

So those are the types of
things that we wanna do.

The other really important thing

for variables such as
that is when these tests

go through the development process

they would typically have a...

you might test, a number
of these variables

and then verify, it matters
or it doesn't matter.

And then you kind of have to set a fairly

strict protocol for, using this container,

this device, et cetera, et
cetera, this time of the day,

all of those things kind
of get into that protocol.

And then when you move
forward it minimizes

that variability when it
comes to, the actual results.

- Yeah. I'm gonna get myself

in trouble here when I ask this.

But would that be considered part of

the matrix, or the matrix
is just the specimen itself?

Not exactly all the, like you said,

collection parameters around it.

- So yeah, when we think of matrix

we think the specimen itself, but from

the total test process, we
don't wanna be blind to it.

I actually just attended
a pre-analytic meeting

that the American Association
for Clinical Chemists puts

on last week and it's
dedicated to that entire,

especially pre-analytic
being from time of order to

at least by the time the
sample gets collected

or really tested on the instrument.

There's a lot of things
that goes into that.

And it's one of the primary
areas that contributes

to testing errors as we
think of them in medicine

about 70% of errors occur in
that pre-analytic time period.

So I don't like to isolate
the matrix sample alone.

It's important to, expand the scope and

and not be blinded to those other impacts.

- I'm so glad you mentioned that stat 70%

of errors happening in
that pre-analytical phase.

So that makes me think another population

that is our audience is clinicians.

And so I'm kind of curious,
could you kind of elaborate

maybe unpack those pre-analytic
variables that like

a clinician may have kind of
top of mind or what might be

in their kind of sphere of
control, influence, awareness.

- Yeah. So things that we think of

in that phase that a
clinician could directly

possibly impact are
ordering the right test.

So sometimes we call tests confusing names

and so we wanna make
sure that we're actually

ordering the right test
and it's not confusing.

And then when, a lot of
the errors that we see

in the laboratory are related to labeling.

So actually making, verifying
the patient's identification

printing a label at
bedside and only that label

and a fixing it to the sample and,

making kind of closing the loop

and making sure that there's no other,

pre-printed labels that could be

in the environment that could

accidentally be placed on it, et cetera.

And then from there it's
transporting the sample

to where it gets tested, under

the conditions that are specified.

So again, that goes back to
how stable is the sample.

Can it be exposed to light air?

All of those things that you have to work

out when we validate these tests.

And so making sure
there's a system in place

so that you know how to do what
you need to do is important.

And then really from
there, the laboratory kind

of takes over and there's routing

and pre-processing and other things can,

that could go wrong,
that we try to mitigate.

- That's awesome and I think not only

does that give people
kind of some thoughts

to reflect on, but also, I mean,

it really resonates with
my experience before I got

into pathology as a medical student.

I had no idea of this kind of,

this nuances complexity
of what things were named.

I think that's largely 'cause my world

as a young medical student
was a lot more simple.

It was just that maybe CBC's
and complete metabolic panels.

But as life has gone on testing

has gotten more and more complex.

For the laboratorians, our kind of

third population listening,
I'm kind of curious,

you mentioned some of these
things like, sometimes

we call something a confusing
name, things like that.

What's your advice to the
laboratory professionals

that are listening about how we can be,

how we can detect when these kinds

of things are going awry or
how, how do you keep your finger

on the pulse of, how your colleagues

on the clinical side are using your tests?

- Yeah, no, it's an excellent question

and a hard one to answer, honestly,

I think really looking
at utilization patterns

can be kind of something that
we can use as sort of a flag.

If you have a really high volume of a test

that you sort of aren't expecting,

or maybe you're spending a lot
of money sending out a test.

You can start questioning,
go to the top users

and ask them, what do
you do with this result,

et cetera, et cetera and ask some of

those questions, really, to

educate yourself if nothing else.

And then when it comes
to actual test naming

there are initiatives out
there to try and standardize

our names for orderable tests so that,

the medical student that goes

onto a residency somewhere else

and then a fellowship
possibly somewhere else

and then practices medicine at,

various institutions, you don't have to

relearn medicine, every time
you take a step in your career.

So actually this is kind of
in that informatic space.

There's a gal, Dr. Ila
Singh, who leads a Truulab.

I'm not gonna be able to
tell you what that stands

for T R U U L A B
initiative, which is actually