Transcript Oral HPV-related cancers and the dentist`s role - Dana

Oral HPV-Related Cancers and the
Dentist’s Role
Alessandro Villa, DDS, PhD, MPH
Division of Oral Medicine and Dentistry
Brigham and Women’s Hospital, Boston
Dana-Farber Cancer Institute, Boston
Department of Oral Medicine, Infection and Immunity
Harvard School of Dental Medicine, Boston
Disclosure
I, Alessandro Villa, have been asked to disclose any significant
relationships with commercial entities that are either providing financial
support for this program or whose products or services are mentioned
during my presentations.
I have no relationships to disclose (or disclose relationships).
I may/will discuss the use of vaccines in a manner not approved by the
U.S. Food and Drug Administration, but in accordance with ACIP
recommendations
Objectives
• Identify the relationship between HPV and head
and neck cancers
• Familiarize with the risk factors, signs and
symptoms of HPV-related head and neck cancers
• Describe the role of oral health care providers in
the prevention and diagnosis of HPV-related head
and neck cancers
Head and neck cancer
Head and neck cancer: risk factors
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Cigarette smoking (less with other tobacco)
Alcohol (synergistic)
Areca nut (India)
Immunosuppression (pts with cancer, HIV)
Family history of cancer
HPV (OP– which ones?)
Age
Sunlight
Plummer Vinson syndrome (iron deficiency anemia,
esophageal webs, oral ca)
Scully C et al., 2009
D’Souza et al., 2007
Oral HPV and cancers
1983
2000
Oropharyngeal cancer
• 48,330 new cases
are expected in the
United States in
2016
• > 70%: HPV infection
American Cancer Society, 2016
HPV and the oral cavity
Disease
HPV Type
OP cancer
16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58,
69, 66, 68, 73
Squamous papilloma
6, 11
Verruca vulgaris
2, 4, 6, 40, 57
Condyloma acuminatum
6, 11, 42, 43, 44, 53, 54, 55, and others
Focal epithelial hyperplasia
13, 32, 55
OPMD (?)
Oral HPV infection
Persistent infection
Oral Oncol. 2015 Mar;51(3):229-36
HIM study
Int J Cancer. 2015 Jun 15;136(12):2752-60.
Does HPV-16 detection precede the
incidence of OPC?
• 96,650 participants, cancer free at baseline, with available
mouthwash samples; 2 prospective cohort studies
• Incident cases of HNSCC (n = 132) (f/u: 3.9 years)
• Oral HPV-16 detection was associated with incident HNSCC
(OR, 7.1; 95% CI, 2.2-22.6) + positive association for
oropharyngeal SCC (OR, 22.4; 95% CI, 1.8-276.7)
HPV-16 detection precedes the incidence of OPC
JAMA Oncol. 2016 Jan 21
Role of HPV after cancer treatment
All participants with persistent oral HPV16 DNA detected after treatment
experienced disease recurrence
JAMA Oncol. 2015;1(7):907-915
Incidence trends over the past 2
decades (1992-2012)
4
3.5
Lip, -4.7*
2.5
Oral tongue, 0.8*
2
Other mouth, -2.4*
Salivary gland, 0.6
1.5
OP, 1.6*
Other pharynx, -3.3*
1
*p<0.05
0.5
0
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Rate per 100,000
3
Incidence trends stratified by sex
(1992-2012)
Men
Women
Oral tongue, 0.4
4
Other mouth, -2.7*
3
Salivary gland, 0.8
2
OPC, 2.1*
1
0
Other pharynx, -3.3*
*p<0.05
Rate per 100,000
Lip, -5.5*
5
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
2012
Rate per 100,000
6
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
Lip, -2.6*
Oral tongue, 1.4*
Other mouth, -2.2*
Salivary gland, -0.2
OPC, -0.7*
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
2012
7
Other pharynx, -3.9*
*p<0.05
HPV and OPC
• The incidence of HPV-related OSCC continues
to increase in North America and Western
Europe
• Up to 70% of new OPC cases in the US are
attributed to HPV
• Data from the developing world remain
lacking
Laryngoscope, 126:894–900, 2016
Risk factors for oral HPV infection
Increased risk of HNC
for:
– number of sexual
partners [OR=1.29,
95% CI: 1.02-1.63]
(19 studies)
– number of oral sex
partners [OR=1.69,
95% CI: 1.00-2.84]
(5 studies)
JCO 2015;33:3235-3242
Cancer Epidemiol. 2015;39(6):1036-46
HPV and SCC
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Fasting-growing type of SCCa in men under age 40
Mostly HPV-16
Mostly tonsillar
Highly-associated with number of sex partners regardless
of sexual preference
• Better prognosis than conventional SCCa
J Dent Res. 2009 Apr; 88(4): 300–306
Prev Med. 2011 Oct 1; 53(Suppl 1): S5–S11
HPV + and HPV - SCC
HPV +
HPV -
Younger age (<45)
Older age (>50)
Increasing incidence
Stable incidence
Frequently basaloid, nonkeratinizing,
poorly differentiated SCC
Frequently keratinizing SCC
Predominantly oropharynx (tonsil and
tongue base)
All head and neck sites
Better survival
Worse survival
More radiosensitive
Higher rates of patients presenting with
nodal metastases and SCC of unknown
primary
Adv Genet. 2016;93:1-56
HPV + OPC signs/symptoms
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A sore throat that does not go away
Trouble swallowing
Trouble opening the mouth fully
Trouble moving the tongue
Ear pain
A lump in the back of the mouth, throat, or neck
A change in voice
Coughing up blood
Enlarged lymph nodes or weight loss
ADA, statement and NCI
Role of HPV in non-OPC?
Oral Oncol. 2014 May;50(5):370-9
HPV-associated epithelial dysplasia
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20 cases (7 men, 3 women); median age 56 years
All had the exact same unusual dysplasia
All were high risk HPV positive, p16 positive
20% developed HPV-positive SCC
What does it mean?
• Unsure how many cases exist
• All but two cases were HPV-16
(unpublished)
• Will prognosis be better?
HPV Vaccines
Bivalent
2vHPV
(Cervarix)
Quadrivalent
4vHPV
(Gardasil)
9-Valent
9vHPV
(Gardasil 9)
Manufacturer
GlaxoSmithKline
Merck
Merck
HPV Types Included
16, 18
6, 11, 16, 18
6, 11, 16, 18,
31, 33, 45, 52, 58
Contraindications
Hypersensitivity
to latex*
Hypersensitivity
to yeast
Hypersensitivity
to yeast
3 dose series:
0, 2, 6 months
2 dose series 11-12 yo:
0, 6 months
3 dose series 15-26 yo:
0, 2, 6 months
Dose Schedule
3 dose series:
0, 1, 6 months
FEMALES 9-26 and MALES 9-26 (off label)
* May be present in tip of pre-filled syringes
Oral protection in women?
J Natl Cancer Inst (2016) 108(1): djv302
Oral protection in men?
• 3 doses of Gardasil.
• Saliva and serum tested for anti–HPV-16 and
anti–HPV-18 antibodies + total IgG levels.
• 100% developed detectable serum anti-HPV16 and anti-HPV-18 antibodies, and most had
detectable antibodies in both oral specimen
types at month 7 (93% and 72%).
J Infect Dis. 2016 Oct 15;214(8):1276-83.
Why the dental professionals?
• Oral cancer screening examinations
• Frequent visit compared to other health
care providers
• Evidence of dentists playing a preventative
role has been demonstrated in the area of
tobacco cessation
Asian Pacific Journal of Cancer Prevention.2015 16(10) 4429-4434
Public Health. 2014 March; 128(3): 231–238
Why the dental professionals?
Dentists make a significant difference
• Educating on HPV
• Explaining that HPV causes oro-pharyngeal
cancers
• Showing how to perform oral cancer
screenings
• Referring patients to get vaccinated
Public Health. 2014 March; 128(3): 231–238
Initial reluctance from dentists
• Immunizations not normally discussed in health
history
• Limited knowledge on the topic
• Discomfort with discussing STIs
• Insufficient time during appointments
• Scope of practice concerns
Public Health. 2014 Mar;128(3):231-8
Medical History
• Include a question on immunizations in
general:
– “Are you (or your child) current on all
immunizations, including HPV?”
– “Would you like a link to or printout of the
current CDC immunization schedule?”
– www.cdc.gov/vaccines
Explaining HPV
• “HPV is a virus that can cause cancers in
several parts of the body, including the mouth
and throat.”
• “There is a vaccine for HPV that can help
prevent these cancers. It works really well
and fewer people are getting HPV-related
cancers because of it.”
• “We’ll be doing an oral cancer screening today
and will teach you how to do self-screenings
at home.”
Explaining HPV Vaccine
• “The vaccine is most effective for people ages
10-14 (all genders; better immune response),
and most insurances cover it for ages 9-26.”
• “Adults over 26 can still pay out of pocket.”
• “The vaccine is very safe. It is as safe as all
other vaccinations. Controversy comes from
claims not founded in science, and I
recommend vaccination to all of my patients.”
Explaining HPV Vaccine
• Remind patients that it is given in 3 doses
(or 2 depending on age).
• Referrals to go to their PCP, health clinic,
pharmacist, or other immunization
provider.
• Encourage parents and patients to keep
you updated with their injection dates.
To summarize
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HPV primarily causes oropharyngeal cancer
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Different from squamous cell carcinoma (SCC) of the
oral cavity
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Some support that HPV can also cause oral SCC
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Screening for oropharyngeal cancer is mainly done
by asking patients questions about their symptoms
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HPV vaccination may offer oral protection