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More testing, more

I
n early 2014, a 48-year-old man visited his dentist for a routine visit. After
Loretta Sullivan-Chang, MD; Mona
the dental examination, his dentist offered him a new “3-in-1 swish and
Saraiya, MD, MPH; Eileen F. Dunne,
gargle” test to see if he might have, or be at risk of developing,
MD, MPH; John T. Brooks, MD
oropharyngeal cancer. The only information the dentist provided was
that the human papillomavirus (HPV) subtype polymerase chain reaction test
would help evaluate for the presence of HPV infection, an emerging cause of
throat cancer. The patient agreed to the test, and the result was positive for
HPV-16. Cytologic examination of his specimen demonstrated no pathological
changes. Fluorescence in situ hybridization results showed normal copy
numbers of chromosomes and did not detect amplification of the genes TERC,
TERT, or CCND1. The dentist charged the patient approximately $100 for the
test; when the patient’s insurance denied the claim, the test manufacturer
waived the charges.
Because of the positive HPV test result, the dentist referred the patient to
an otolaryngologist, who performed nasopharyngolaryngoscopy (NPL); ex-
amination findings were unremarkable. The cost of this visit, including the
NPL, was approximately $2,000. The patient’s otolaryngologist recom-
mended quarterly follow-up visits with NPL. The patient later discovered
that his health insurer did not agree with the indication for his visit to the
otolaryngologist, so he paid much of the cost of the visit out of pocket.
For screening to be effective, several criteria need to be met, including the
following: a disease that is an important health problem; a disease that has a
long precancerous phase (oropharyngeal cancer has no precancerous phase)
for which the natural history of the condition is well known; a screening test
that is accurate, affordable, and acceptable; and a disease for which treatment
is available to treat the precancerous phase before it progresses to cancer.1 For
cervical cancer, the long-term experience of the Papanicolaou test fulfills
many of the criteria of screening.1 Ever since investigators found HPV
infection to be a necessary condition for developing cervical cancer, testing
for the oncogenic HPV types has received much attention. Results from
several large-scale randomized trials in which the investigators used high-
grade cervical cancer as an endpoint support initiation of HPV-based
screening for cervical cancer as a more effective form of screening than is
cytologic examination. Since 2012, the US Preventive Services Task Force

JADA 148(11) http://jada.ada.org November 2017 781

(USPSTF) recommended the HPV these tests, nor have the USPSTF or There is no recommended
test to be used with the Papanicolaou the American Dental Association clinical indication for oral HPV
test for screening.2 In 2014, the US recommended them.8,9 These oral screening to evaluate the risk of
Food and Drug Administration HPV tests are considered laboratory- developing oropharyngeal cancer,
(FDA) approved an HPV test for developed tests (LDTs). LDTs his- and there is no FDA-approved
primary cervical cancer screening,3 torically included low-risk simple test. Oral HPV infection preva-
and the USPSTF is reviewing the diagnostics run in a single institu- lence may be common, but its
evidence for this indication. For tion, but LDTs have become more precise role in the pathogenesis of
oropharyngeal cancer and HPV- complex; they may use components oropharyngeal cancer has not been
based screening, we are not there yet.
Clinicians diagnose approxi- There is no recommended clinical indication for
mately 11,000 HPV-attributable oral human papillomavirus screening to evaluate
oropharyngeal cancers each year, the risk of developing oropharyngeal cancer
and most of these are caused by
HPV-16.4 Testing samples from
tissue registries, Chaturvedi and that are not FDA regulated, and in- defined. The use of unapproved
colleagues2 demonstrated that HPV stitutions and private companies are oral HPV tests could result in
prevalence in oropharyngeal cancers using them increasingly.10 harm without any proven benefit.
in the United States increased from In our vignette, the positive Detection of HPV (not cancer)
16% in the 1980s to 72% during HPV test result from the dental through oral screening may result
the 2000s. From 1988 to 2004, visit created substantial anxiety and in invasive procedures of uncertain
population-level incidence of HPV- led to many questions. Was it safe value, the potential for provoking
positive oropharyngeal cancers more for the patient to kiss other people patient anxiety, and extra costs, as
than doubled, and HPV-negative (could he pass on the virus and our vignette demonstrated. Oral
cancers decreased by 50%.2 cause cancer in someone else)? HPV tests add to the growing
The natural history of HPV and How likely was it he would develop number of available oral cancer
oropharyngeal cancers has not been cancer? Would the results of the tests that are marketed to dentists
well characterized; notably, in- test and subsequent NPL reduce his or primary care physicians for
vestigators have determined no likelihood of developing cancer and routine screening of patients
detectable precancerous phase.3 improve his chances of survival without symptoms but that have
Among US men and women aged 14 should he develop cancer? Since not been shown to improve out-
to 69 years, the prevalences of any the original test, he has undergone comes.9 Understanding of the risk
oral HPV and of HPV-16 infection 4 additional quarterly NPLs and is and potential consequences of
were 6.9% and 1.0%, respectively.5 in discussion with his otolaryngol- overdiagnosis is especially impor-
Oral HPVs, including type 16 and ogist about the frequency of the tant for health care providers in an
other oncogenic types, likely clear examinations. environment in which patients
within 18 months after an infection.3 Although HPV may be trans- often rely on social media or the
In contrast to our understanding mitted via oral sex or deep kissing, Internet as their source of infor-
regarding HPV and cervical cancer, there are no data to support oral mation.11 Primary prevention
we have much less information HPV transmission through casual through widespread HPV vaccina-
about the natural history of HPV social contact. Little is known about tion, which is recommended for
and oropharyngeal cancer.3,6 the risk of developing oropharyngeal use in both boys and girls aged 11
With the increased awareness and cancer associated with an oral HPV or 12 years, is likely the best
publicity that HPV infection can infection, which has a high likeli- strategy for reducing HPV-
cause oropharyngeal cancer, manu- hood of clearing, and whether an attributable oropharyngeal can-
facturers7 have developed oral HPV invasive procedure such as NPL re- cers.12 n
tests and marketed them to health duces the likelihood of developing http://dx.doi.org/10.1016/j.adaj.2017.08.023
care providers, including dentists, cancer. Rigorous prospective studies
dental hygienists, and primary care characterizing the likelihood of and Copyright ª 2017 American Dental
physicians. The test kits recommend preventable risk factors for devel- Association. All rights reserved.
testing annually, although there are oping oropharyngeal cancer are Dr. Sullivan-Chang was pursuing oncology
no data to support that testing once, lacking, and we are unaware of any specialty training at Stanford University School
or more often, will decrease the data supporting the use of tests that of Medicine, Stanford, CA, when this article was
risk of developing or dying from are not FDA approved to reduce written. She is now associate medical director,
Oncology Early Development at The Janssen
oropharyngeal cancer. More impor- morbidity or mortality from Pharmaceutical Companies of Johnson & John-
tantly, the FDA has not approved oropharyngeal cancer. son, Spring House, PA.

782 JADA 148(11) http://jada.ada.org November 2017

Dr. Saraiya is a medical epidemiologist, Divi- screening for cancer: hope and hype. Nat Rev. 7. OralDNA Labs. OraRisk HPV. Available at:
sion of Cancer Prevention and Control, Centers Clin Oncol. 2016;13(9):550-565. http://www.oraldna.com/oral-hpv-testing.html.
for Disease Control and Prevention, CHAM Bldg 2. Chaturvedi AK, Engels EA, Pfeiffer RM, Accessed January 17, 2017.
107 Rm 04288, Mailstop F76, Atlanta, GA 30329, et al. Human papillomavirus and rising 8. Moyer VA. Screening for oral cancer: U.S.
e-mail yzs2@cdc.gov. Address correspondence to oropharyngeal cancer incidence in the United Preventive Services Task Force recommendation
Dr. Saraiya. States. J Clin Oncol. 2011;29(32):4294-4301. statement. Ann Intern Med. 2014;160(1):55-60.
Dr. Dunne is a medical epidemiologist, Divi- 3. Gooi Z, Chan JY, Fakhry C. The epidemi- 9. Rethman MP, Carpenter W, Cohen EE,
sion of HIV/AIDS Prevention, Centers for ology of the human papillomavirus related to et al. Evidence-based clinical recommendations
Disease Control and Prevention, Atlanta, GA. oropharyngeal head and neck cancer. Laryngo- regarding screening for oral squamous cell
Dr. Brooks is a medical epidemiologist, Divi- scope. 2016;126(4):894-900. carcinomas. JADA. 2010;141(5):509-520.
sion of HIV/AIDS Prevention, Centers for Dis- 4. Saraiya M, Unger ER, Thompson TD, et al; 10. Lazarus TS, Chaihorsky L. The metrics of
ease Control and Prevention, Atlanta, GA. HPV Typing of Cancers Workgroup. US change: the impact of the FDA’s pending LDT
assessment of HPV types in cancers: implica- regulation. MLO Med Lab Obs. 2014;46(12):
Disclosure. None of the authors reported any tions for current and 9-valent HPV vaccines. 28-29.
disclosures. J Natl Cancer Inst. 2015;107(6):djv086. 11. Glick M. Prevention, screening, and
5. Gillison ML, Broutian T, Pickard RK, a chance of rain. JADA. 2015;146(4):
The findings and conclusions in this report are et al. Prevalence of oral HPV infection in the 217-218.
those of the authors and do not necessarily United States, 2009-2010. JAMA. 2012;307(7): 12. Petrosky E, Bocchini JA Jr, Hariri S, et al.
represent the official position of the Centers for 693-703. Use of 9-valent human papillomavirus (HPV)
Disease Control and Prevention. 6. Berman TA, Schiller JT. Human papillo- vaccine: updated HPV vaccination recommen-
mavirus in cervical cancer and oropharyngeal dations of the advisory committee on immuni-
1. Shieh Y, Eklund M, Sawaya GF, Black WC, cancer: one cause, two diseases. Cancer. 2017; zation practices. MMWR Morb Mortal Wkly
Kramer BS, Esserman LJ. Population-based 123(12):2219-2229. Rep. 2015;64(11):300-304.

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