1. HPV vaccine — what is known and unknown!
Dr. Abdelrahman Ezzat
MB BCh, MSc (ENT), MRCS, DOHNS, MBA (Hosp)& FEB-ORLHN

2. Items HP virus Incidence and Epidemiology Socioeconomic assessment
Public Policy and Public Health
Vaccination
Good Morning.
I have a special task today, which is HPV and what is known and unknown!.
What I will try, (in a short time) , to give you an overview on Background of HPV vaccine

3. HPV- Background ~ 200 genotypes of the virus 13 high-risk types.
HPV 16 , 18 play a major role in cancer
HPV 6 and 11 can lead to respiratory and ano-genital warts.
At the current state of research, around 200 genotypes of the virus have been identified.
Those include 13 high-risk types.
HPV 16 and 18 play a major role in cancer development, whereas HPV 6 and 11 can lead to respiratory and anogenital wart

4. oropharyngeal cancer. N Engl J Med. 2010; 363:24–35.
First, HPV is a non-enveloped DNA virus.
The HPV genome ,Contain different protein codes as shown in the upper figure
the role of E6 and E7 proteins in cancer is shown in the lower figures
Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with
oropharyngeal cancer. N Engl J Med. 2010; 363:24–35.

5. HPV-Related Diseases
HPV-Related Diseases

6. Head and neck -Squamous cell carcinoma (HNSCC)
4% of all malignancies in the United States
~17 per 100,000 persons per year
~30,000 Oropharyngeal cancers
HPV is detected in ~25% of all HNSCC
Head and neck -Squamous cell carcinoma (HNSCC) is one of the most important disease related
HN-SCC 4% of all malignancies in the United States
HN- SCC Incidence is ~17 per 100,000 persons per year
~30,000 oropharyngeal cancers new case every year ,
HPV is detected in ~25% of all HNSCC
Nasman A, Attner P, Hammarstedt L, et al. Incidence of human papillomavirus (HPV) positive
tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer.
2009; 125:362–366.

7. World incidence rates of HNSCC
Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB, editors. Cancer incidence in five continents, vol. VIII. Lyon: IARC Scientific Publications No. 155 IARC; 2002.

8. HN-SCC risk factors HNSCC and Smoking Age: Most common > 50’s
Race/ethnicity
Blacks > whites
HNSCC and Smoking
the overall incidence has been declining
Age : Most common in or after 50’s
Race/ethnicity
Blacks > whites
Over the past 20 years, the overall incidence of head and neck Squamous cell carcinoma (HNSCC) has been declining in the United States, a decline which has been attributed to a decrease in the prevalence of smoking
Auluck A, Hislop G, Bajdik C, et al. Trends in oropharyngeal and oral cavity cancer incidence of
human papillomavirus (HPV)-related and HPV-unrelated sites in a multicultural population: the
British Columbia experience. Cancer. 2010; 116:2635–2644.
sturgis EM, Cinciripini PM. (2007). Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer 110:

9. Sexual behavior
Oropharyngeal cancer cases have a higher average number of lifetime sexual partners
more likely to have current oral HPV infection
Increased risk with
>6 partners,
>4 oral sex partners
earlier age at 16
Case–control studies consistently show that oropharyngeal cancer cases have a higher average number of lifetime sexual partners and are more likely to have current oral HPV infection than matched controls
Increased risk with >6 partners, >4 oral sex partners and earlier age at 16
Heck JE, Berthiller J, Vaccarella S, et al. Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE)
consortium. Int J Epidemiol. 2010; 39:166–181.

10. A-Oral and Oropharyngeal Cancer
HPV is an etiological cause of these oropharyngeal cancers.
HPV is a major cause of oropharyngeal cancer in developed countries, detected in 45–90% of cases.
B- Laryngeal Cancer
HPV Identified in % of biopsies from separate studies
There is strong and consistent molecular evidence demonstrating that HPV is an etiological cause of these oropharyngeal cancers.
In fact, HPV is now the major cause of oropharyngeal cancer in developed countries, detected in 45–90% of cases.
HPV Identified in % of biopsies from separate studies
Betiol J, Villa LL, Sichero L. Impact of HPV infection on the development of head and neck cancer. Brazilian Journal of Medical and Biological Research. 2013;46(3):

11. Betiol J, Villa LL, Sichero L
Betiol J, Villa LL, Sichero L. Impact of HPV infection on the development of head and neck cancer. Brazilian Journal of Medical and Biological Research. 2013;46(3):

12. C-Recurrent Respiratory Papillomatosis
new cases each year with an incidence of 0.5–4 per 100,000.
In Children:
4.3 cases per 100,000 children
Peak at 2-3 yrs
Often firstborn of young mothers of low economic status
Male = female
In Adults
1.8 per 100,000 in adults
Peak at yrs
Males > females (4:1
new cases each year with an incidence of 0.5–4 per 100,000 .
In Children:
4.3 cases per 100,000 children
Peak at 2-3 yrs
Often firstborn of young mothers of low economic status
Male = female
In Adults
1.8 per 100,000 in adults
Peak at yrs
Males > females (4:1 (Larson and Derkay, 2010). )
Larson DA, Derkay CS. Epidemiology of recurrent respiratory papillomatosis. APMIS. 2010;
118:450–454.

13. D-Cervical Cancer HPV as necessary cause of cervical cancer 1995/1996
~492,800 cervical cancers caused worldwide by HPV each year,
HPV as necessary cause of cervical cancer was proved in 1995/1996
~492,800 cervical cancers caused worldwide by HPV each

14. World incidence rates of cervical cancer 2002
Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002 cancer incidence. Mortality and prevalence worldwide. IARC CancerBase No. 5 version 2.0. Lyon: IARC Press; 2004.

15. Knowledge about HPV
In USA: knowledge of HPV was generally very limited among Hispanic > black>Asian >white.
In the UK, : more educated people had better knowledge of the established risk factors
In Germany: association with social class (high is lower)
In Turkish :no association between HPV knowledge and educational level.
In USA: knowledge of HPV was generally very limited among Hispanic > black>Asian >white.
In the UK, : more educated people had better knowledge of the established risk factors
In Germany: association with social class
In Turkish :no association between HPV knowledge and educational level.
Giorgi Rossi P, Baldacchini F, Ronco G. The Possible Effects on Socio-Economic Inequalities of Introducing HPV Testing as Primary Test in Cervical Cancer Screening Programs. Frontiers in Oncology. 2014;4:20.

16. NIU Galway -Student Awareness Study Human Papilloma Virus (HPV) Knowledge
Answered: 1, Skipped: 49
NIU Galway -Student Awareness Study about HPV by Prof KOEGH team shows
45% student don’t know HPV

17. Did you know certain types of HPV (16&18) are associated with developing Head and Neck Cancer?
It also shows that 83 % of the student don’t know relation between HPV and HN SCC

18. Years of Potential Life Lost (YPLL)
Cancer-specific estimates (2003)
45,815 YPLL for oral cavity/oropharyngeal cancer in M
17,773 for oral cavity/oropharyngeal in F
Years of potential life lost (YPLL), is a measure of premature mortality.
Cancer-specific estimates (2003) in USA
45,000 YPLL for oral cavity/oropharyngeal cancer in M (lowest was 3,654 YPLL for penile cancer)
17,773 for oral cavity/oropharyngeal in F (range of 5,000 YPLL for vaginal cancer to 80,000 YPLL for cervical cancer)
For more information on NCHS and its NVSS, visit

19. Vaccination Both Quadrivalent (Gardasil®) and bivalent FDA-approved
In2006 : first licensed for use in females ages 9–26 years old
In 2010: expanded to also include males in this age range
Both Quadrivalent (Gardasil®) (HPV6,11,16,18) and bivalent (HPV16 and 18) FDA-approved
Quadrivalent vaccine had 98% efficacy
first licensed in 2006 for use in females
In 2010 expanded to also include males

20. No much diffferant

21. U.S. vaccine recommendations
vaccine recommendations for the U.S. population.
all female adolescents ages 11–12 years receive the vaccine as part of routine care, with a “catch up”
vaccination for females ages 13–26 years who had not been previously vaccinated,
vaccination available for females as young as age 9 if they were felt to be at high risk for infection
The Advisory Committee on Immunization Practices (ACIP)
vaccine recommendations for the U.S. population.
ACIP recommended that all female adolescents ages 11–12 years receive the vaccine as part of routine care, with a “catch up” 2 doses
vaccination for females ages 13–26 years who had not been previously vaccinated,
vaccination available for females as young as age 9 if they were felt to be at high risk for infection

22. The two-dose schedule for Gardasil® is licensed for individuals aged 9 up to and including 13 years of age and
Cervarix® is licensed for individuals aged 9 up to and including 14 years of age.
In 2013/14, both Gardasil® and Cervarix® received licensing approval from the European Medicines Agency (EMA) for a two-dose schedule in adolescent girls.
The two-dose schedule for Gardasil® is licensed for individuals aged 9 up to and including 13 years old and
Cervarix® is licensed for individuals aged 9 up to and including 14 years old.
JCVI has agreed, however, to recommend a two-dose schedule up to (and including) 14 years of age for both Cervarix® and Gardasil®.

23. Prevalence of HPV Before and after immunization in England

24. Prevalence of HPV Before and after immunization in Australia
HIV, viral hepatitis and sexually transmissible infections in Australia Annual Surveillance Report 2015

25. Public Policy and Public Health
The HSE (2014) states that:
“In Ireland 660,000 doses of Gardasil® have been administered and more than 200,000 girls have been fully vaccinated against HPV.

26. Public Policy and Public Health Impact of high versus low vaccination coverage
A variety of mathematical models have been used to estimate HPV vaccines’ impact on HPV-related disease incidence, prevalence and costs.
Which show that, it is highly cost-effective
A variety of mathematical models have been used to estimate HPV vaccines’ impact on HPV-related disease incidence, prevalence and costs.
Which show that, it is highly cost-effective
Cost-effectiveness of female human papillomavirus vaccination in 179 countries: a PRIME modellingstudy. Lancet Glob Health. 2014 Jul;2(7):e

27. Public Policy and Public Health Long term vaccine efficacy?
Several longer-term trials are currently underwent to evaluate the vaccines’ effectiveness against anogenital cancers.
No clinical trials able to assess directly the HPV vaccine impacts on HN-SCC.
Several longer-term trials are currently underwent to evaluate the vaccines’ effectiveness against anogenital cancers.
No clinical trials able to assess directly the HPV vaccine impacts on HN-SCC.
Romanowski B. Long term protection against cervical infection with the human papillomavirus:
review of currently available vaccines. Hum Vaccin. 2011; 7

28. Public Policy and Public Health Are there rare adverse events?
Clinical trials have demonstrated that both vaccines are well tolerated, with safety profiles
Clinical trials have demonstrated that both vaccines are well tolerated, with safety profiles
Lu B, Kumar A, Castellsague X, et al. Efficacy and safety of prophylactic vaccines against cervical
HPV infection and diseases among women: a systematic review & meta-analysis. BMC Infect Dis.
2011; 11:13.

30. Vaccination in male Quadrivalent approved by FDA March 2010
Males 9-26 yrs
However, not deemed ??/and ??? cost-effective
Is it cost-effective to vaccinate females only ??

31. Summer and recommendation
There are lack of knowledge about HPV related HNSCC among population , so we need to raise the profile of HNSCC and its risk factors.
We need long term studies evaluate the efficacy of the vaccine against HNSCC
Male vaccination should be evaluated to cut the cycle of infection in heterosexual, bisexual and specially in Homosexual partners.

32. Thank you
Questions
Abdelrahman Ezzat