olfactory detection of human cancer by dogs. a review of research and results

Olfactory Detection of Human Cancer by Dogs:

A Review of Research Studies and Results

Naomi O’Donoghue

BAAF2

Dundalk Institute of Technology

Naomi O’Donoghue Olfactory Detection of Human Cancer by Dogs BAAF2

2

ContentsIntroduction...........................................................................................................................................1

Methodology.........................................................................................................................................2

The Results............................................................................................................................................2

Untrained pets detectives...............................................................................................................2

Pickel et al. (2004).........................................................................................................................3

Willis et al. (2004).........................................................................................................................3

McCulloch et al. ( 2006)................................................................................................................4

Horvath et al. (2008)......................................................................................................................4

Gordon et al. (2008).......................................................................................................................5

Horvath et al. (2010a)....................................................................................................................5

Cornu et al. (2011).........................................................................................................................6

Sonoda et al. (2011).......................................................................................................................6

Elliker et al. (2014)........................................................................................................................7

Discussion and Recommendations........................................................................................................7

References.............................................................................................................................................9

Bibliography........................................................................................................................................10

Webography........................................................................................................................................10

Appendix 1..........................................................................................................................................11

Table 1: Methods of Canine Training Compared...................................................................11

Appendix 2..........................................................................................................................................12

Table 2: Results of Studies Compared...................................................................................12

Introduction

Every year, across the world, billions of dollars are invested into curing and preventing

cancer; the world’s leading cause of death. Advanced screening and detection methods are

developed and new drugs and technologies are trialled to help fight the many forms of this

disease. Yet still, the number of deaths caused by cancer continues to grow. Current figures

show that approximately 8 million people die from cancer each year and the World Health

Organisation predicts that this figure will increase 80% by 2030 (Centers for disease Contol

and Prevention, 2014).

Early detection may be man’s greatest from of defence. However, this is often difficult as

screening techniques can be expensive and in some cases are not without their own health

risks. In order to encourage people to seek regular care, less invasive, and simpler methods

would be advantageous, especially if they can prove to be more sensitive and accurate in

detecting early stages of cancer. This demand has led to many alternative methods and

technologies being explored.

The theory that dogs may be able to detect human cancer using their superior olfactory

system is one such alternative that has been widely researched in recent years. A dog’s sense

of smell is said to be anywhere from 1000 to 10,000 times more sensitive than humans.

Research has already shown that a dog can sense when an epileptic person is going to have a

seizure or when a diabetic’s blood glucose level drops. This is due to the dog’s ability to

smell pheromones or chemical changes taking place in the body (Spake, 2008).

Extensive training and tests have been carried out to discover if dogs can also be trained to

identify and detect human cancers. Findings from these studies have prompted scientists to

ask: what is it exactly that the dog can smell? Does cancer have a distinguishing odour

signature made up of Volatile Organic Compounds (VOCs) which are emitted into the air?

And if this chemical compound could be isolated and replicated then might it be possible to

develop an electronic nose which could potentially mimic the dog’s olfactory sense? It is

hoped to explore these ideas and attempt to answer the questions posed.

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Methodology

This review has been conducted to ascertain the validity of the hypothesis that dogs can smell

and be trained to smell cancer with a degree of accuracy great enough for diagnostic purposes

and worthy of an endeavour to replicate their skill electronically. Significant studies from the

past decade were explored. Efforts were made to include those studies which tested the

canine’s ability to identify a variety of cancers. Nine relevant studies were chosen under these

criteria. The contrasting training techniques, sample tissues used, and testing conditions were

examined and the results compared. The recorded accounts of untrained pet dogs who

“sniffed out” cancer in their owners have been included for comparison as they acted as the

catalyst for all future research into this topic.

The Results

Untrained pets detectives

Several cases tell the story of how pet dogs alerted their owners to the existence of cancer. It

began in 1989 with a letter to the British medical journal, the Lancet, which highlighted the

story of a woman who had been assured that a blemish on her upper leg was just a mole. Her

pet dog, showing an extraordinary interest in the mole, persisted in sniffing it for prolonged

periods and eventually tried to bite it off. This motivated the women to seek a dermatologist’s

opinion and a malignant melanoma was discovered. The authors were compelled to suggest

that the melanoma must have given off a scent that the dog could detect (Williams &

Pembroke, 1989).

Many years later, a man who had eczema on his leg for over 18 years had it re-examined after

his pet dog showed a bizarre interest in, and constantly sniffed at the lesion. Again it was

discovered to be cancer (Church & Williams, 2001). In yet another example, a pet dog poked

and nudged at its owners left breast until finally the women discovered a lump which a

biopsy later revealed as cancerous. In this case the dog’s interest never waned despite

mastectomy, chemotherapy and radiation, and the woman died a year later (Welsh, et al.,

2005).

What is important to note from these stories is that the dogs were not trained, there was no

reward for correct identification and the cancers were of different varieties. This possibly

suggests that the odour was so strong and at odds with what the dogs perceived as normal and

healthy that it provoked such a reaction. The intriguing potential of these claims led to the

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numerous research studies to discover if dogs can definitely sniff out cancer and if the odour

emitted is from the cancer itself or manifested by the bodies attempt to fight against the

disease.

Pickel et al. (2004)

This study tested the ability of dogs to detect melanoma in real patients. Dogs were first

trained to recognise the scent of melanoma tissue cells and to associate this with praise from

the handler. The several stages of training showed promising results and so testing

commenced. (Please refer to Appendix 1 for a simple comparison of the training methods

used in all nine studies examined).

The final test stage involved seven real patients who were covered in a number of bandages,

one of which concealed the suspicious target area of skin. Dog A found the correct target on

six out of seven patients but failed to recognise any melanoma on the other. Dog B had a

success rate of three out of four and similarly did not identify any melanoma on the same

patient as Dog A. These results were deemed significant and the failure of both dogs on the

same patient showed consistency in their scent detection (Pickel, et al., 2004). The test

conditions displayed some flaws, however. It was not a double blind test and the patients or

the person who placed the bandages could have given the dog hints or cues. It can also be

argued that the numbers in the test group were too small. If healthy control patients had been

added and the dogs had correctly identified no target area it would have given more validity

to the results. One criticism is that the dogs’ response may not necessarily be to the actual

cancer, as one must examine a dog’s treatment of cuts or sores on their own skin and how

they often lick lesions on an owner. The changes in the skin itself may simply emit an odour

that the dog finds unusual (Horvath, et al., 2008).

Willis et al. (2004)

A “proof of principle study” was carried out to establish if dogs could successfully be trained

to locate bladder cancer with more accuracy than would be expected by “chance alone”

(Willis, et al., 2004). Urine samples were used in testing and controls were taken from both

healthy and diseased subjects. Efforts were made to attempt to match controls to cancer

samples as close as was possible by age and sex. They also included control samples from

patients who suffered with other urological disorders. This made for more accurate testing

conditions as any difference in scent that the dog picked up would be most likely due to the

cancer and not any other variable.

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The dogs as a group had a success of 41% while mere chance was calculated at 14% (Willis,

et al., 2004). Their hypothesis was proven as the success rate was well over the probability of

it being just luck. (Please see Appendix 2 which compares the resulting data from all nine

studies in tabular form).

The study raises the issue of whether urine is the most appropriate sample to use in testing

and the training methods and selection of the dogs are open to criticism. Results, none the

less, showed positive findings that bladder cancer has an odour signature that dogs can

identify. Of particular note, and pointed out in the commentary of Cole, (2004), was that all

of the dogs indicated one control patient sample as positive for bladder cancer. This was of

such interest to the physician that tests were carried out on the subject and kidney cancer was

later discovered (Cole, 2004).

McCulloch et al. ( 2006)

This study proved that household dogs could be quickly trained to detect breast and lung

cancer using breath samples; that these dogs could discriminate cancerous samples over those

from control subjects; and that the dogs accuracy was unaffected by variables such as the

stage the cancer was at or whether the subject was a smoker (McCulloch, et al., 2006).

Sensitivity is the percentage of cancer targets that the dog correctly identifies, while

specificity is the percentage of control subjects that the dog correctly ignores. For the lung

cancer trials dogs scored 99% for both sensitivity and specificity. For breast cancer, results

were 88% and 98% respectively. This was the one of the first tests that showed such

successful and definitive results. One criticism was that the control samples used were all

from healthy individuals. Had controls been obtained from subjects with other non-cancerous

lung or breast conditions, sensitivity results may not have been so inflated (Moser &

McCulloch, 2010). Or perhaps, the dogs performance would have remained as high and more

credence could be attributed to their ability.

For experimental purposes, three patients who were in remission were used as control

samples. The dogs, however, indicated one of these controls as a cancerous target in 96% of

tests. A year and a half after the study the dogs’ diagnosis was confirmed, as breast cancer

was found to have recurred (McCulloch, et al., 2006).

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Horvath et al. (2008)

Cancers such as ovarian carcinoma have unfavourable survival rates, which is why it is so

important to discover new techniques for early detection. Horvath et al. (2008) undertook

this study to examine the detection rate of ovarian cancer by trained sniffer dogs in a bid to

discover if the cancer has a specific signature. They argued that while results from previous

studies were encouraging, there was no definitive proof that the dogs were in fact receiving a

scent emitted directly from the cancer or if they were responding to other smells associated

with the body’s fight against it.

Moreover, they wanted to establish not only if the dogs could detect the cancer but if they

could then distinguish it from other gynaecological cancers. The dog’s sensitivity level was

an amazing 100%, detecting every target scent even when presented with other ovarian tissue

as controls. Their findings also indicate that ovarian carcinoma has a distinct and significant

odour which is different to other gynaecological cancers (Horvath, et al., 2008).

Gordon et al. (2008)

This study did not obtain the levels of success they had anticipated. Urine samples from

patients of breast and prostate cancer were used but the dogs in the tests did not show

significant detection rates. By their own admission, a more rigorous training discipline may

have produced better results. Each dog was trained at the trainers own home which allowed

for potential distractions and dogs were merely chosen on the basis of what breed the trainer

owned (Gordon, et al., 2008). Trainers did not work together and no regular or regimented

design was put in place which caused a lack of uniformity to occur. In a systematic review of

these 5 initial studies, Moser and McCulloch (2010) suggested that the discrepancies in the

training techniques adopted “may have made it nearly impossible for the dogs to perform

well” (Moser & McCulloch, 2010, p. 151).

Horvath et al. (2010a)

Building on their success and what was learned from the 2008 study; new tests were carried

out to include blood samples as well as tumour tissue samples. Again, they displayed an

efficient and apparently effective dog training technique. They proved that dogs can

differentiate between the blood from an ovarian cancer patient and the blood from a patient

suffering from other related cancers, “such as endometrial, cervical and vulvar carcinoma”

(Horvath, et al., 2010a). With these results the authors indicate that the distinguishing scent

discharged from the carcinoma is also detectable in the blood.

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In another study by the author they successfully showcased the performance of an electronic

nose based on their 2008 findings that each cancer has a unique volatile organic compound.

The objective was for the device to detect, as the dog had, the ovarian carcinoma tissue

against healthy ovarian tissue based on the VOC that was being emitted. A sensitivity of

84.4% was achieved and a specificity of 86.8% (Horvath, et al., 2010b). Continuation studies

such as these, which build on the successes of previous work, contribute some of the most

significant data and results.

Cornu et al. (2011)

This study added to the now increasing list of cancers that dogs can be trained to detect.

Successful results were obtained for canine detection of prostate cancer, with both significant

sensitivity and specificity achieved (91% each). Theories established by previous studies that

perhaps urine was not an effective sample for use in testing could be dismissed with the

performance of the dog in this trial.

The training period and methods were thorough and a wide range of urine samples were used.

All 108 samples were given by men who has a biopsy of the prostate performed, the results

from which distinguished the cancer targets from controls. Of the 33 tests performed the dog

wrongly identified 3 control samples as targets. These were re-examined and 1 control

patient was found to have prostate cancer (Cornu, et al., 2011).

Sonoda et al. (2011)

While this study set out to train the dog to detect colorectal cancer, in the course of training

the dog learned to identify several cancer types. Initial training began with breath samples of

oesophageal cancer. The dog was allowed to smell the breath sample from the oesophageal

patient and then was instructed to find the cup which contained the same breath sample

amongst 4 control samples. This was repeated over the following days using lung cancer and

gastric cancer samples. In the next stage of training any 1 of those 3 cancer samples were

used at random. This then advanced to a stage where the dog was allowed to smell the sample

from 1 cancer and tasked to find another cancer type amongst the controls. Other cancer

types were introduced over time and by the end of training the dog could identify 12 different

forms of cancer (Sonoda, et al., 2011).

For both sample types a specificity of 99% was achieved and a sensitivity of 91% and 97%

respectively was achieved for breath and watery stool samples. Notably, results for colorectal

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cancer in its early stage were also very precise. The excellent results and the advanced

training techniques suggest that much had been learned from previous studies.

Elliker et al. (2014)

In this most recent study, ten dogs were trained to identify prostate cancer. Several stages of

training took place followed by three test periods. While significant results were achieved in

training, levels of success in the actual tests were extremely poor. Only two dogs were

deemed good enough to progress to the test phase.

Sensitivity and specificity ratings achieved in the test period by the first dog were 13% and

71% respectively, and 25% and 75% for the second dog. The researchers believed that the

failure of the dogs to identify in tests what they could previously identify in training was

down to the fact that the dogs were not familiar with the new samples presented during the

test runs. 50 prostate cancer samples were used over the course of the training phase. They

suggest that the dogs may have “memorised the odour of each individual donor’s urine during

training” instead of learning the scent associated with the cancer in general (Elliker, et al.,

2014). The study by Cornu et al. (2011) discredits this theory that the dog memorised targets

samples, as 26 cancers were used during their training phase, and when the new, unfamiliar

samples were introduced in the testing phase, the dogs still achieved sensitivity of 91%.

In one stage of testing the dogs were rewarded whether they detected the target or not, as no

one in the room knew where the sample target lay. This was rectified in the next stage but

the author acknowledged that the dog’s decision making may have been confused by this

error which could have contributed to the poor success rates. The only other study examined

that displayed such poor results was Gordon et al. (2008) which similarly tested prostate

cancer using urine and also used 10 dogs in training. It is widely acknowledged that the poor

results were most probably due to the poor training structure, so this may also be the case in

this study. The failure of so many of the dogs to even make it past the training stage could

point to an ineffective training technique.

Discussion and Recommendations

Nine scientific studies and three anecdotal stories of dogs detecting human cancers have been

reviewed throughout this report. The primary objective was to discover if dogs could be

trained to detect human cancers and the overall combined findings reveal that they can.

Some studies displayed far superior training techniques and their results reflected this effort

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with much greater success rates. Most studies used the reward-based clicker method to train

the dogs, which proved sufficient where it was adopted appropriately. The data does not

reveal any one breed, sex or age profile of dogs that showed the best results. Indeed, it is

difficult to compare the studies in this regard as successes or failures cannot solely be

attributed to the dog in isolation, but the many other variables such as design of training,

samples used and testing conditions must also be considered.

It was hoped to establish if each cancer contains volatile organic compounds and a unique

chemical signature. Several of the studies claimed evidence of this to be true. However,

while we now know of their existence, research has still not been able to decipher what

exactly this chemical make-up is. The establishment of a more concrete breakdown of

chemical configurations and biomarkers was expected by this author due to the profound

leaps forward in science and technology over the last twenty years. However, data found in

this area was somewhat disappointing. Still, advances are being made which will undoubtedly

lead to a break-through in the future.

With regard to the sample types used, the exhaled breath and tumour tissue appears to give

the highest success rates. This author would suggest that breath samples may be the most

advantageous, non-invasive and cost effective means of cancer testing if the work that is

being carried out on electronic noses continues to a prototype stage. Results from the Horvath

et al. (2010b) study incite confidence that the dogs’ sense of smell will one day be fully

replicated with substantial sensitivity. Perhaps in the future, blowing into a cancer

breathalyser will be a routine procedure carried out at every G.P. visit and cancers will be

caught at their early stages.

These studies all stemmed from one occurrence where a dog potentially saved its owners life

by sniffing out a skin cancer (Williams & Pembroke, 1989). A significant number of cases

were found where volunteers who had simply given samples to be used as controls were

discovered to have cancer. These people may be alive today due to the fact that this research

is being carried out. So, while cancer sniffing dogs may not yet have advanced to the stages

where they are being used in practical work conditions like other explosive and narcotic

sniffer dogs, they have, none-the-less, already started their life saving work. One is left in no

doubt that dogs really are man’s best friend!

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References

Centers for disease Contol and Prevention, 2014. Cancer Prevention and Control. [Online] Available at: http://www.cdc.gov/cancer/dcpc/resources/features/worldcancerday/[Accessed 02 April 2014].

Church, J. & Williams, H., 2001. Another sniffer dog for the clinic?. Lancet, Volume 358, p. 930.

Cole, T., 2004. Commentary: Teaching dogs new tricks. BJM, Volume 329, p. 718.

Cornu, J. et al., 2011. Olfactory Detection of Prostate Cancer by Dogs Sniffing Urine: A Step Forward in Early Diagnosis. European Association of Urology, 59(2), pp. 197-201.

Elliker, K. et al., 2014. Key considertions for the experimental training and evaluation of cancer odour detection dogs: lessons learnt from a double-blind, controlled trial of prostate cancer detection. BMC Urology, Volume 14, p. 22.

Gordon, R. et al., 2008. The Use of Canines in the Detection of Human Cancers. The Journal of Alternative and Complementary Medicine, 14(1), pp. 61-67.

Horvath, G., Andersson, H. & Paulsson, G., 2010a. Characteristic odour in the blood reveals ovarian carcinoma. BMC Cancer, Issue 10, p. 643.

Horvath, G., Chilo, J. & Lindblad, T., 2010b. Different volatile signals emitted by human ovarian carcinoma and healthy tissues. Future Oncology, 6(6), pp. 1043-1049.

Horvath, G., Jarverud, G., Jarverud, S. & Horváth, I., 2008. Human Ovarian Carcimona Detected by Specific Odor. Integrative Cancer Therapies, Issue 7, pp. 76-80.

McCulloch, M. et al., 2006. Diagnositc Accuracy of Canine Scent Detection in Early- and Late-Stage Lung and Breast Cancers. Integrative Cancer Therapies, 5(1), pp. 30-39.

Moser, E. & McCulloch, M., 2010. Canine scent detection of human cancers: A review of methods and accuracy. Journal of Veterinary Behavior, Issue 5, pp. 145-152.

Pickel, D. et al., 2004. Evidence for canine olfactory detection of melanoma. Applied Animal Behaviour Science, Volume 89, pp. 107-116.

Sonoda, H. et al., 2011. Colorectal cancer screening with odour material by canine scent detection. Gut, 60(6), pp. 814-819.

Spake, A., 2008. Could a Dog Save Your Life?. [Online] Available at: http://www.diabetesforecast.org/2008/mar/could-a-dog-save-your-life.html[Accessed 06 April 2014].

Welsh, J., Barton, D. & Ahuja, H., 2005. A case of breast cancer detected by a pet dog. Community Oncology, Issue 2, pp. 324-326.

Williams, H. & Pembroke, A., 1989. Sniffer dogs in the melanoma clinic?. Lancet, Volume 1, p. 734.

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Willis, C. et al., 2004. Olfactory detection of human bladder cancer by dogs: proof of principle study. BMJ, Volume 329, pp. 712-718.

Bibliography

Balseiro, S.C. & Correia, H.R., 2006. Is olfactory detection of human cancer by dogs based on major histocompatibility complex-dependent odour components? – A possible cure and a precocious diagnosis of cancer. Medical Hypotheses, 66, pp. 270-272.

King, C.R. 2006. Dogs May Be Able to Detect Cancer. Oncology Nursing Forum, 33(1), pp.21-22.

Lippi, G. 2011. Letter to the Editor. European Association of Urology, 60(4), p. 29

Roine, A. et al., 2012. Detection of smell print differences between nonmalignant and malignant prostate cells with an electronic nose. Future Oncology, 8(9), pp. 1157-1165.

Siegel, R., Naishadham, D. and Jemal, A. 2013. Cancer statistics, 2013. CA: A Cancer Journal for Clinicians, 63(1), pp. 11–30.

Webography

Cancer Research UK, 2014. Transitional cell cancer of the kidney (renal pelvis) or ureter and its treatment. [Online] Available at: http://www.cancerresearchuk.org/cancer-help/about-cancer/cancer-questions/transitional-cell-cancer-kidney-ureter-treatment[Accessed 7 April 2014].

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Appendix 1

Table 1: Methods of Canine Training Compared

Breed of Dog(s)Age and Sex of

dog

Number of Dogs trained and used

in testing

Dog’s previous training history

Method of dog training

Length of training

Picket et al.(2004)

Standard SchnauzerRetriever Bitch

4 year old male6 year old bitch

2Certified bomb

detection dog andMaster Hunter

Not indicatedSeveral weeks andLess than several

weeks

Willis et al.(2004)

Variety of breeds Not indicated 6No previous search or

scent trainingClicker training 7 months

McCulloch et al.(2006)

3 Labrador retrievers

2 Portuguese water dogs

7-18 months3 dogs, 2 bitches

5 No previous trainingFood reward-based

clicker training2-3 weeks

Horvath et al.(2008)

Riesenschnauzer 4 years old 1 Not indicatedResembled sniffer

dog training12 months – twice

per week

Gordon et al(2008)

Various Breeds 2-8 years old 10Most had previous

trainingClicker training with

food reward12-14 months

2-7 times per week

Horvath et. al.(2010)

Black Giant Schnauzer

7 year old bitch3 year old bitch

2

Previously trained to detect ovarian

carcinomaNo previous training

Resembled sniffer dog training

9 months

Cornu et. al.(2011)

Belgian Malinois Shepherd

Young Dog 1 No previous trainingClicker Training with ball reward

24 months – 5 days per week

Sonoda et. al.(2011)

Labrador retriever 8 year old bitch 1Trained in water

rescue and then as a cancer detection dog

Play reward-based approach

Not indicated

Elliker et. al(2014)

7 different breeds1-11 years old

4 bitches and 6 dogs10 and 2

No previous odour detection training

Food reward-based clicker training

5-13 months

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Appendix 2

Table 2: Results of Studies Compared

Cancer tested Sample type Structure of testSensitivity / Specificity

or Success rateCancer : Control

Picket et. al.(2004)

Melanoma Melanoma tissue cells Single Blind 75-85.7% success 1:7-29

Willis et. al.(2004)

Bladder Urine and dried urine Single Blind 41% success 1:6

McCulloch et. al.(2006)

Lung and Breast Exhaled breath Double Blind 99/99% and 88/98% 1:4


Ovarian Tumour tissue Double Blind 100/97.5% 2:8

Gordon et. al(2008)

Breast and Prostate Urine Blinded but unspecified22/18% Sensitivity and

17% success1:6


Ovarian Blood and tumour tissue Double Blind 100/98% and 100/95% 1:5

Cornu et. al.(2011)

Prostate Urine Double Blind 91/91% 1:5

Sonoda et. al.(2011)

ColorectalExhaled breath and

watery stool samplesDouble Blind 91/99% and 97/99% 1:4

12


Elliker et. al(2014)

Prostate Urine Double Blind 13/1% and 25/75% 1:3

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olfactory detection of human cancer by dogs. a review of research and results

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