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

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

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

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.

HPV-Related Diseases HPV-Related Diseases

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.

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.

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 110:1429-1435

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.

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 10 -50% 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 10 -50% 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):217-226.

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):217-226.

C-Recurrent Respiratory Papillomatosis 1500-2500 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 20-40 yrs Males > females (4:1 1500-2500 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 20-40 yrs Males > females (4:1 (Larson and Derkay, 2010). ) Larson DA, Derkay CS. Epidemiology of recurrent respiratory papillomatosis. APMIS. 2010; 118:450–454.

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

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.

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.

NIU Galway -Student Awareness Study Human Papilloma Virus (HPV) Knowledge Answered: 1,533 Skipped: 49 NIU Galway -Student Awareness Study about HPV by Prof KOEGH team shows 45% student don’t know HPV

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

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 http://www.cdc.gov/nchs.

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 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm095647.htm

No much diffferant

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

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®.

Prevalence of HPV Before and after immunization in England http://vk.ovg.ox.ac.uk/hpv-vaccine

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

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.

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):e406-14.

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

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.

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 ??

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.

Thank you Questions Abdelrahman Ezzat