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VPH / displasia oral /epidemiología del cáncer
Laia AlemanyPrograma de Recerca en Epidemiologia del Càncer
Insitut Català d’Oncologia
16 Octubre 2019
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Contents
1. Natural history: from oral HPV infection to head andneck cancer (HNC)
2. Epidemiology: attributable fractions, burden, trends,age-gender issues
3. Prevention: HPV vaccines
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Contents
1. Natural history: from oral HPV infection to head andneck cancer (HNC)
2. Epidemiology: attributable fractions, burden, trends,age-gender issues
3. Prevention: HPV vaccines
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Head and neck regions
HPV: human carcinogen
OropharynxTonsil(Hematoxylin-Eosin)
HNC
PenisAnus
CervixVaginaVulva
HPV-related cancers
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Institut Català d’Oncologia
NORMALORAL MUCOSA
ORAL HPV INFECTION
PRECANCEROUSLESIONS
HEAD AND NECK CANCER
TIME
RISK FACTORS FOR INFECTIONPERSISTENCE AND
PROGRESSION TO CANCER
RISK FACTORS FOR HPV INFECTION
HPV LIFE CYCLE
PERSISTENCE &PROGRESSION
CLEARANCE REGRESSION
TRANSMISSION OFHPV INFECTION INVASION
SURVIVAL, RECURRENCIES,
ETC
TREATMENT
PROGNOSTIC FACTORS
¿ ?
The natural history: from an oral HPV infection to HNC
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Institut Català d’Oncologia
The natural history: from an oral HPV infection to HNC
NORMALORAL MUCOSA
ORAL HPV INFECTION
RISK FACTORS FOR HPV INFECTION
HPV LIFE CYCLE
TRANSMISSION OFHPV INFECTION
Prevalence of oral HPV infection in cancer-free subjects: • 4.5% (95%CI:3.9-5.1%) – [systematic review, 18 studies, n subjects-
4,581, search up to June/2009; Kreimer AR et al. STDs. 2010]
• 4.0% (95%CI:3.1-5.0%) – [HIM study-Brazil, Mexico, USA, n subjects-1,680 (age: 18-74 yo); Kreimer AR et al. CEBP. 2010]
• 6.9% (95%CI:5.7-8.3%) – [NHANES-USA, n subjects-5,579, (age: 14-69 yo); Gillison ML et al. JAMA. 2012]
• HPV16 the most common type
Associated factors:• Older ages• Men• Tobacco use• Sexual behavior (number of sexual partners, …)
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Institut Català d’Oncologia
The natural history: from an oral HPV infection to HNC
NORMALORAL MUCOSA
ORAL HPV INFECTION
RISK FACTORS FOR HPV INFECTION
HPV LIFE CYCLE
TRANSMISSION OFHPV INFECTION
Prevalence of oral HPV infection in cancer-free subjects:
• New meta – 50 studies, 30,000 subjects.4.9% overall-1% HPV16[Mena M et al. JID 2019]
• Meta on MSM (HIV + vs -) [King EM et al. PlosOne. 2016]:
HIV- HIV+Overall 17.1 (7.3-26.8) 28.9 (19.1-38.7)HR 9.1 (4.0-14.2) 16.5 (8.2-24.8)HPV16 3.0 (0.5-5.5) 4.7 (2.1-7.3)
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Institut Català d’Oncologia
The natural history: from an oral HPV infection to HNC
NORMALORAL MUCOSA
ORAL HPV INFECTION
RISK FACTORS FOR HPV INFECTION
HPV LIFE CYCLE
TRANSMISSION OFHPV INFECTION
Prevalence of oral HPV infection in cancer-free subjects-SPAIN:
• Students 18-25 yo, Valencia 2012-2013; 543 –vaccinees (10%- 4.1-19.5% - non typeable) vsnon-vaccinees (6.8%- 4.7-9.4% - 60% HR types) [Diez J et al. Vaccine 2019]
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Institut Català d’Oncologia
NORMALORAL MUCOSA
ORAL HPV INFECTION
PRECANCEROUSLESIONS
HEAD AND NECK CANCER
TIME
RISK FACTORS FOR INFECTIONPERSISTENCE AND
PROGRESSION TO CANCER
RISK FACTORS FOR HPV INFECTION
HPV LIFE CYCLE
PERSISTENCE &PROGRESSION
CLEARANCE REGRESSION
TRANSMISSION OFHPV INFECTION INVASION
SURVIVAL, RECURRENCIES,
ETC
TREATMENT
PROGNOSTIC FACTORS
¿ ?
The natural history: from an oral HPV infection to HNC
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Institut Català d’Oncologia
The natural history: from an oral HPV infection to HNC
Leemans R et al. Nature Reviews, 2018
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Institut Català d’Oncologia
The natural history: from an oral HPV infection to HNC
Leemans R et al. Nature Reviews, 2018
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Institut Català d’Oncologia
Contents
1. Natural history: from oral HPV infection to head andneck cancer (HNC)
2. Epidemiology: attributable fractions, burden, trends,age-gender issues
3. Prevention: screening-E6 HPV serology / HPVvaccines
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ICO international survey, HPV in HNCs
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Cas
tells
agué
/Ale
man
y et
al.
JNC
I, 20
16
24.9
22.4
18.5
7.4
4.4
3.0
5.7
3.5
1.5
AF
AF: Attributable Fraction
HPV detection (%) in HNCs, by biomarkers
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HPV detection (%) variability in Oropharynx
Plummer et al. Lancet Glob Health, 2016
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De
Mar
tel e
t al.
IJC
, 201
7
Age standardized (world) incidence rates (per 100,000) of head and neck cancer cases attributable to HPV. 2012
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De
Mar
tel e
t al.
IJC
, 201
7
Number of cancer cases attributable to HPV, by region and sex. 2012
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Cha
turv
ediA
et a
l. J
Clin
Onc
ol. 2
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Incidence trends in HNCs by site
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Trends of HPV positive cases (US)
OropharynxHPV+
HPV-
Cha
turv
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et a
l. J
Clin
Onc
ol. 2
013
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HPV detection (%) variability in Oropharynx
Com
bes
et a
l. C
EB
P, 2
014
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Trends of oropharyngeal cancersin HIV +
Picard et al. Medicine Maladies Infectieuses, 2018
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Contents
1. Natural history: from oral HPV infection to head andneck cancers (HNC)
2. Epidemiology: attributable fractions, burden, trends,age-gender issues
3. Prevention: HPV vaccines
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Mirghani H, Jung AC, Fakhry C. Eur J Cancer. 2017
Prevention in HPV-oropharyngealcancers
N.Brenner(serology)
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HPV vaccine effect on oral HPV infection and cancer
Main obstacles for designing/including assessment of oral endpoints inHPV vaccine clinical trials:
1. Low oral HPV prevalence
2. Still gaps in knowledge in the natural history: oropharyngeal pre-neoplastic lesions?
By analogy with genitals, it is likely that the vaccines will be alsoeffective against HPV HNSCC
But, which is the available data for HPV vaccines andoral infections?
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Immunology• Studies have shown that HPV vaccination are able to indude high
titers of type-specific oral antibodies in oral fluids:
Rowhani-Rahbar A, JID, 2009 (oral antibodies for monitoring HPVvaccines. Vaccination with 4v vaccine)
Handisurya A, BJC, 2016 (oral antibodies with ability of neutralising HPVpseudovirions – in vitro. Vaccination with 4v vaccine)
Pinto LA, JID, 2017 (HPV vaccination of males with 4v HPV vaccineinduced oral HPV antibody levels that correlate with serum, at month 7)
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Efficacy
• Costa Rica clinical trial
• 7,466 women 18-25yo randomized (1:1) to receive 2v vaccine
• At 4 year visit, 5,840 provided oral specimens to evaluate vaccine efficacyagainst oral infections (VE)
• Oral prevalence for mucosal HPV types was low: 1.7%
• VE oral HPV: 93.3% (63-100%) [15 HPV16/18 oral HPV infections in thecontrol group vs 1 in the vaccinated group]
• Limitations: Lack of baseline information, only women, lower oralexposure?
2013
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Effectiveness
• National Health and Nutrition Examination (NHANES), 2011-2014
• 2,627 participants 18-33yo who indicated whether they had received theHPV vaccine and provided adequate oral sample
• 18.3% received at least 1 dose of HPV vaccine
• Vaccinated adults had a lower oral prevalence of vaccine-types(6/11/16/18) compared to unvaccinated adults (0.11 vs 1.61%; p<0.001)
• Prevalence of non-vaccine types was similar (3.98 vs 4.74%; p>0.05)
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Conclusions
• Oropharyngeal cancers are related to HPV withvariation in the attributable fractions by region
• There is an increasing trend of HPV-relatedoropharyngeal cancers mainly in developed countries
• Prophylactic HPV vaccination should work, but thereare still obstacles in terms of gender-neutralprogrammes, understanding natural history, amongothers
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