VPH / displasia oral / epidemiología del cáncer · 2019-11-18 · oral HPV infection to HNC...

VPH / displasia oral /epidemiología del cáncer

Laia AlemanyPrograma de Recerca en Epidemiologia del Càncer

Insitut Català d’Oncologia

16 Octubre 2019

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

Head and neck regions

HPV: human carcinogen

OropharynxTonsil(Hematoxylin-Eosin)

HNC

PenisAnus

CervixVaginaVulva

HPV-related cancers

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



NORMALORAL MUCOSA

ORAL 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, …)



NORMALORAL MUCOSA

ORAL HPV INFECTION


HPV LIFE CYCLE


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)



NORMALORAL MUCOSA

ORAL HPV INFECTION


HPV LIFE CYCLE


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]


NORMALORAL MUCOSA

ORAL HPV INFECTION

PRECANCEROUSLESIONS

HEAD AND NECK CANCER

TIME

RISK FACTORS FOR INFECTIONPERSISTENCE AND

PROGRESSION TO CANCER


HPV LIFE CYCLE

PERSISTENCE &PROGRESSION

CLEARANCE REGRESSION

TRANSMISSION OFHPV INFECTION INVASION

SURVIVAL, RECURRENCIES,

ETC

TREATMENT

PROGNOSTIC FACTORS

¿ ?




Leemans R et al. Nature Reviews, 2018


Contents

1. Natural history: from oral HPV infection to head andneck cancer (HNC)


3. Prevention: screening-E6 HPV serology / HPVvaccines

ICO international survey, HPV in HNCs

Cas

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/Ale

man

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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

HPV detection (%) variability in Oropharynx

Plummer et al. Lancet Glob Health, 2016

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

De

Mar

tel e

t al.

IJC

, 201

7

Number of cancer cases attributable to HPV, by region and sex. 2012

Cha

turv

ediA

et a

l. J

Clin

Onc

ol. 2

013

Incidence trends in HNCs by site

Trends of HPV positive cases (US)

OropharynxHPV+

HPV-

Cha

turv

ediA

et a

l. J

Clin

Onc

ol. 2

013

HPV detection (%) variability in Oropharynx

Com

bes

et a

l. C

EB

P, 2

014

Trends of oropharyngeal cancersin HIV +

Picard et al. Medicine Maladies Infectieuses, 2018

Contents

1. Natural history: from oral HPV infection to head andneck cancers (HNC)


3. Prevention: HPV vaccines

Mirghani H, Jung AC, Fakhry C. Eur J Cancer. 2017

Prevention in HPV-oropharyngealcancers

N.Brenner(serology)

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?

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)

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

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)

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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