VAKSIN HPV

Andrijono
Subbagian Onkologi, Dept Obstetri Ginekologi FKUI/RSCM
JUMLAH SAMPLE : 20 000
INSIDEN INFEKSI HPV :

INSIDENS INFEKSI HPV ONKOGENIK :

WORLD HEALTH PERPECTIVE
CERVICAL CANCER CONTROL
PROGRAM
VAKSIN HPV
VAKSIN PENCEGAHAN
 VLP

VAKSIN TIDAK MENGANDUNG VIRUS

VAKSIN BERISI BAGIAN KULIT VIRUS YG DIBUAT

ATAU SINTESISNYA
 Active protection via vaccination is mediated by neutralizing
antibodies at the cervix

HPV Neutralizing antibodies

Cervical canal

Cervical
epithelium

Blood vessel

Epithelial tear

Basement membrane

1. Stanley M. Vaccine 2006; 24:S16–S22;

2. Giannini S, et al. Vaccine 2006; 24:5937–5949;
3. Nardelli-Haefliger D, et al. J Natl Cancer Inst 2003; 95:1128–1137;
4. Poncelet S, et al. IPC 2007(poster).
 Composition of HPV Vaccine
Cervarix™
Antigens AS04 adjuvant

+ Aluminium
salt
(Al(OH)3)
+ MPL
Immunostimulant

HPV 16 VLPs HPV 18 VLPs

AS04-containing vaccine

QUADRIVALENT
Antigens Adjuvant

+ Aluminium salt
(amorphous aluminium
hydroxyphosphate
sulphate [AAHS])
HPV 16 VLPs HPV 18 VLPs HPV 6 VLPs HPV 11 VLPs

AAHS-containing vaccine
 Composition of HPV Vaccinesa
GARDASIL™
Human Papillomavirus
Vaccine [Types 6, 11, 16, AAHS
18] (Recombinant, 225 μg
adsorbed)1

6 11 16 18
20 μg 40 μg 40 μg 20 μg

GARDASIL™9 AAHS
Human Papillomavirus 9-valent Vaccine (Recombinant, adsorbed) 2 500 μg

6 11 16 18 31 33 45 52 58
30 μg 40 μg 60 μg 40 μg 20 μg 20 μg 20 μg 20 μg 20 μg

a
For the remainder of the presentation, GARDASIL will be referred to as 4vHPV vaccine and GARDASIL 9 will be referred to as 9vHPV vaccine.
AAHS=amorphous aluminum hydroxyphosphate sulfate; HPV=human papillomavirus; MSD=Merck Sharp & Dohme Corp.
91. GARDASIL [summary of product characteristics]. Lyon, France: Sanofi Pasteur MSD SNC; 2014. 2. GARDASIL 9 [summary of product characteristics]. Lyon, France:
Sanofi Pasteur MSD SNC; 2015.
HALAL
Impact of 4vHPV Vaccine in
Public Vaccination Programs
 Impact of 4vHPV Vaccine in Public
Vaccination Programs: Select Reportsa Genital Warts
Baandrup Ali Wilson Smith
Sex Transm Dis13 BMC Infect Dis16 Sex Transm J Infect Dis24
Infect20
Read
Sex Transm Leval
Infect8 J Infect *Blomberg Ali Chow *Droletc
Dis11 Clin Infect BMJ17 BMJ21 Lancet Infect Dis25
Dis14
Fairley Donovan
Sex Transm Lancet
Flagg Harrison *Petráš
Introduction of 4vHPV vaccine1–6 Infect7 Infect Dis9 Bauer
*Leval
Am J Public
JNCI3 PLoS One22 Vaccine26
Am J Health18
Public
Health12
Oliphant
Mikolajczyk Nsouli-Maktabi Liu *Dominiak-Felden
NZMJ10
Czech Republic Sex Transm MSMR19 Sex Transm PLoS One6
Dis15 Infect23

Cervical
Australia
Abnormalities *Baldur-Felskov *Crowe *Smith
Cancer Causes BMJ31 Pediatrics33
Control30
*Gertig
Brotherton *Powell BMC Med29
New
Canada Lancet27 Vaccine28
Zealand *Baldur-Felskov *Mahmud *Hariri *Herweijer
Sweden
JNCI4 J Clin Oncol32 Vaccine34 Int J
Cancer35
Belgium
United Denmarkb HPV Prevalence
States *Tabrizi Markowitz *Tabrizi Deleré *Dunne *Markowitz
J Infect J Infect Dis37 Lancet BMC Infect J Infect Pediatrics41
Germany Dis40
Dis36 Infect Dis38 Dis39

2006 2007 2008 2009 2011 2012 2013 2014 2015 2016
*Study links effectiveness data to vaccination status aIncludes reports published in the peer-reviewed scientific literature, and does not encompass reports at scientific conferences. bBeginning on February 1,
2016 the childhood vaccination program includes the 2vHPV vaccine. 42 cMeta-analysis of data from 20 studies in 9 countries (United States, Australia, England, Scotland, New Zealand, Sweden, Denmark,
Canada, and Germany), including both 4vHPV vaccine and 2vHPV vaccine. 25
Please see corresponding slide note for references.
 Australia: Cervical Abnormalities
reduction 13

Australia: Population-based analysis of % reduction in cervical Australia: Population-based analysis of percentage reduction in cervical
abnormalities among vaccinated (at least 1 dose) vs contemporaneous abnormalities among vaccinated vs contemporaneous
unvaccinated screened females in Victoria unvaccinated screened females in Queensland
Garland et al; Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of
Real-world Experience: CID, 2016
 Sweden & USA: Cervical Abnormalities
reduction 14

Sweden: % reduction in CIN2+ and CIN3+ among females fully United States: % reduction in HPV 16/18-related cervical abnormalities
vaccinated with 4vHPV vaccine (3 doses) vs unvaccinated /partially among females vaccinated with 4vHPV vaccine (at least 1 dose) vs
vaccinated females, by age at first dose contemporaneous unvaccinated females
Garland et al; Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of
Real-world Experience: CID, 2016
1. HPV – Associated Cancer
 Bladder cancer : 37% Squamous cell carcinoma,
Urothelial cancer

HPV types 16, 18, 31, 33, 52, and 58

Jennifer Rose Chapman-Fredricks, etall. Arch Pathol Lab Med. 2013;137:1088–1093

Kazuyoshi Shigehara , etall. Cancer 2011;117:2067–76 , G Visalli, etall. WCRJ 2018;5(1):E1058
 meta-analysis
Thaisa Pelizzer, etall. Rev. bras. epidemiol. vol.19 no.4 São Paulo Oct./Dec. 2016
Raul D. Bernabe-Dones, etall. Gastroenterology Research and Practice. 2016;8:7896716
 HPV-positive cancer patients showed worse overall survival

Mariarosa Pascale, etall. Disease Markers Volume 35 (2013), Issue 6, Pages 607–613
 Never smokers – ever smokers
33.9% - 39.2%

EGFR mutation
LUNG
Estrogen as Promoter
Cancer
Human papilloma virus in
non-small cell lung cancer
in never smokers: A systematic
review of the literature

Yoshikazu Hasegawa, etall. Lung Cancer 83 (2014) 8–13

 3. HPV and Oropharyngeal Cancer (OPC)

• Risk factors:
 Traditional- tobacco, alcohol and betel
nut
 Emerging- HPV infection
• 70% of oropharyngeal cancers in the US
are HPV-related squamous cell
carcinomas
Lewis A, Kang R, Levine A, Maghami E. The New Face of Head and Neck
Cancer: The HPV Epidemic. Oncology (Williston Park). 2015 Sep;29(9):616-26.
` ` Males 4X
↑
than
women
Men are less likely to clear oral
HPV infection
(less effective immune response).
Majority clear the virus within 2
years
 HPV-Associated Oropharyngeal Cancers Are
Rising in the United States1

225%
increase
50%
decrease

Based on data from 3 cancer registries (Hawaii, Iowa, and Los Angeles, California).
1. Chaturvedi AK et al. J Clin Oncol. 2011;29:4294–4301. 24
 The Incidence of HPV-Related Tonsillar Cancers
Has Doubled in Recent Decades in Sweden1
Estimated Prevalence of HPV in Tonsillar SCC Cases Diagnosed in Stockholm, Sweden, 1970–2006
1.5
HPV positive
HPV negative
Age-Standardized Incidence Rate
(per 100,000 Person-Years)

1.0

0.5

0.0
1970–1979 1980–1989 1990–1999 2000–2006
Calendar Years
Tonsillar cancer is a subcategory of oropharyngeal cancers.
The study comprised all cases (N=120) of tonsillar SCC in the county of Stockholm from the hospital database of the Karolinska University Hospital in Stockholm between 2003 and
2007; the proportion of HPV-positive tonsillar SCC from 2003 through 2007 was compared with the proportion of cases reported from 1970 to 2002. Of the 120 identified cases, 98
(n=76 males, n=22 females) diagnostic pretreatment tumor biopsies could be obtained by investigators.
SCC=squamous cell carcinoma.
1. Näsman A et al. Int J Cancer. 2009;125:362–366.
HPV and Oropharyngeal Squamous Cell Carcinoma
(OPSCC)
• In 2012, the International Agency for Research on
Cancer (IARC) stated that HPV type 16 causes
cancer of the oropharnynx. 1
• There are no validated or FDA approved tests to
evaluate for precancerous OPSCC lesions (such as the
Papanicolaou test and HPV DNA testing for cervical
cancer)2
• No associated signs or symptoms. Presenting
Symptoms can be: neck mass (only 18% of patients
with HPV OPSCC presented with this symptoms), sore
throat, dysphagia, visualized mass, globus sensation,
odynophagia, otalgia3
• No treatment for active oral HPV infection4
• A detailed review of systems and physical
examination remain the most important method for
early detection2

1. World Health Organization. IARC monographs on the evaluation of carcinogenic risks to humans: volume 100B-Biological Agents. A
review of human carcinogens. Lyon: International Agency for Research on Cancer 2012.
2. Moore KA 2nd, Mehta V. J Am Board Fam Med. 2015 Jul-Aug;28(4):498-503.
3. Mcllwain WR, et al. JAMA Otolaryngol Head Neck Surg 2014; 140:441-7
4. Lewis A, Kang R, Levine A, Maghami E. The New Face of Head and Neck Cancer: The HPV Epidemic. Oncology (Williston Park). 2015
Sep;29(9):616-26
Cervical carcinogenesis
 peripheral blood mononuclear cell

SQUAMOUS CELL CARCINOMA OF THE CERVIX

SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK CANCER

increased with advancing disease stage

15.4% in women with regressed lesions to 38.9% in women with HSIL

PLoS ONE 12(11): e0188592. https://doi.org/ 10.1371/journal.pone.0188592

 HPV-DNA TEST (BLOOD)

STUDY

120 SAMPLE
34,2% (41/120) HPV-DNA TEST IN BLOOD : POSITIVE
HPV45 : 46.3% , HPV51 : 29.6% , HPV16 :18.5%
HPV16 : POSITIVE URINE AND BLOOD
 HPV-DNA TEST (URINE)

META ANALYSIS

16 ARTICLES (14 STUDIES, 1443 SAMPLE)

SENSITIVITY HPV-DNA TEST URINE : 87% (78%-92%)
SPECIVITY HPV-DNA TEST URINE : 94% (82%-98%)
SENSITIVITY HPV-DNA ONCOGENIC HPV : 77% / 88%
SENSITIVITY HPV-DNA HPV16/18 : 73% / 98%
 SUMMARY HPV VACCINE

ONCOPROTEIN
RISK FOR CANCER
HPV infection : local and systemic diseases
These viruses are stable
Sexual transmission and non sexual
HPV-Hr are oncogenic viruses
Screening HPV infection are HPV-DNA test
by smear, blood and urine