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

Contents

Head and neck regions

HPV: human carcinogen

OropharynxTonsil(Hematoxylin-Eosin)

PenisAnus

CervixVaginaVulva

HPV-related cancers

Institut Català d’Oncologia

NORMALORAL MUCOSA

ORAL HPV INFECTION

PRECANCEROUSLESIONS

HEAD AND NECK CANCER

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,

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

RISK FACTORS FOR INFECTIONPERSISTENCE AND

PROGRESSION TO CANCER

HPV LIFE CYCLE

PERSISTENCE &PROGRESSION

CLEARANCE REGRESSION

TRANSMISSION OFHPV INFECTION INVASION

SURVIVAL, RECURRENCIES,

TREATMENT

PROGNOSTIC FACTORS

Leemans R et al. Nature Reviews, 2018

Contents

3. Prevention: screening-E6 HPV serology / HPVvaccines

ICO international survey, HPV in HNCs

AF: Attributable Fraction

HPV detection (%) in HNCs, by biomarkers

HPV detection (%) variability in Oropharynx

Plummer et al. Lancet Glob Health, 2016

Age standardized (world) incidence rates (per 100,000) of head and neck cancer cases attributable to HPV. 2012

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

Incidence trends in HNCs by site

Trends of HPV positive cases (US)

OropharynxHPV+

HPV detection (%) variability in Oropharynx

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)

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?

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

http://ico.gencat.cat

ICO l’HospitaletHospital Duran i ReynalsAv. Granvia de L’Hospitalet, 199-20308908 L’Hospitalet de Llobregat

ICO BadalonaHospital Germans Trias i PujolCtra. del Canyet s/n08916 Badalona

ICO GironaHospital Doctor TruetaAv. França s/n17007 Girona

@ICOnoticies www.facebook.com/ICOnoticies

ICO Camp de Tarragona i Terres de l’EbreHospital Joan XXIIIC. Dr. Mallafrè Guasch, 4 43005 TarragonaHospital Verge de la CintaC. de les Esplanetes, 14 43500 Tortosa

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

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