2009-2010 HPV Abstract Summaries & Research Priorities

403–445 Ellice Avenue Winnipeg, Manitoba, Canada R3B 3P5 T 204.946.0908 F 204.946.0927 www.icid.com

November 2010

© Copyright 2010 International Centre for Infectious Diseases 403–445 Ellice Avenue Winnipeg, Manitoba, Canada R3B 3P5 T 204.946.0908 F 204.946.0927 www.icid.com

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INTRODUCTION The International Centre for Infectious Diseases (ICID) is a Canadian not-for-profit organization that brings people and resources together to find new ways to fight infectious diseases worldwide. The Canadian Network on HPV Prevention is a program of ICID committed to optimizing disease prevention strategies and technologies and improving evidence-based decision-making in public health. The HPV Research Priorities Abstract Summary 2005-2008 was produced to update Canada’s HPV community about HPV research priorities identified at the National HPV Vaccine Research Priorities Workshop (2005) and Master Class (2006). Human papillomavirus research and knowledge continues to advance our understanding of the role and impact of HPV infections worldwide. HPVs represent the most common infectious agents that are transmitted sexually throughout the world. The 2009-2010 HPV Abstract Summaries and Research Priorities provides an update on HPV research published in scholarly journals between January 2009 and September 2010. More than 2,000 articles were reviewed to identify the final 245 abstract summaries contained in this document. Each section of the Abstract Summary contains a brief synopsis of the relevant literature. Interesting areas for further HPV exploration have been identified in certain sections. The 2009-2010 HPV Abstract Summaries and Research Priorities organizes the most current literature into major HPV topics beginning with the Epidemiology of HPV by disease site followed by Primary Interventions, Immunization, Screening, Data Management, Therapeutic Use of Vaccine, and HPV Testing Technology. The contents of this pdf document can be reviewed in whole, by section of interest, or searched by subject matter of interest. The International Centre for Infectious Diseases and the Canadian Network on HPV Prevention would like to acknowledge the contributions of Dr. Allan Ronald and Dr. Alberto Severini for their expert reviews and analysis of articles. In addition, a special thank you to Dr. Allan Ronald for his direction and commitment to the production of this document. This document will continue to be updated on a regular basis and made available in electronic form through the International Centre for Infectious Diseases. Contact Information International Centre For Infectious Diseases 403-445 Ellice Avenue Winnipeg, Manitoba, R3B 3P5 Phone: 204.946.5159 Email: [email protected] Web: www.icid.com

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Table of Contents KEY FINDINGS

....................................................................................................6

SECTION 1. EPIDEMIOLOGY AND BURDEN OF DISEASE......................................8

1.1 Female Genital Cancers and Disease............................................................9



1.1.1 Epidemiology....................................................................................9



1.1.1.1. Incidence and Prevalence..................................................9



1.1.1.2 Linkage with Cervical Screening...................................... 17



1.1.1.3 Multiple HPV Infections...................................................20



1.1.1.4 HPV Persistence.............................................................. 21



1.1.2 Burden of Disease..........................................................................23



1.1.3 Risk Factors...................................................................................28



1.2 Anal Cancer and Disease.............................................................................31



1.2.1 E pidemiology.................................................................................31



1.2.1.2 HPV Duration and Clearance...........................................33

1.2.2 Burden of Disease.........................................................................35

1.3 H ead and Neck Cancer................................................................................36



1.3.1 E pidemiology ................................................................................36



1.3.2 Burden of Disease ........................................................................36



1.4 P enile Cancer...............................................................................................44



1.4.1 Epidemiology.................................................................................44

1.5 O ther Possible Cancers...............................................................................45



1.5.1. Lung Cancer . ...............................................................................45



1.5.2. Breast Cancer ..............................................................................46



1.6 HIV and HPV – Epidemiology and Prognostic Linkages............................... 47



1.6.1 Epidemiology................................................................................. 47

1.7. Recurrent Respiratory Papillomatosis.........................................................56



1.7.1 Epidemiology..................................................................................56



1.8 G enital Warts...............................................................................................60



1.9 W hat other conditions are associated with HPV?.......................................64



1.9.1 Warts, Hypogammaglobulinemia, Infections,



and Myelokathexis (WHIM)...........................................................64



1.9.2 Heck’s Disease..............................................................................64



1.10 H PV Transmission......................................................................................65



1.10.1 Oral Sexual Behaviors, Virginity,



and New Relationships ................................................................65



1.10.2 Male Circumcision.......................................................................69

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SECTION 2. PRIMARY INTERVENTIONS................................................................ 71

2.1 Behavior

..................................................................................................72



2.2 C ircumcision................................................................................................72

SECTION 3. I MMUNIZATION...................................................................................76

3.1 General

..................................................................................................77



3.2 Vaccine Impact on Cervical Screening Programs........................................84



3.3 Vaccination Choice.......................................................................................92



3.4 Vaccination Strategies – Improving Uptake..................................................93



3.5 Cost



3.6 Knowledge, Attitudes, Beliefs...................................................................102

..................................................................................................94



3.6.1 Public...........................................................................................102



3.6.2 Racial/Cultural Differences.......................................................... 110



3.6.3 Education/Intervention................................................................ 116



3.6.4 Parents........................................................................................ 118



3.6.5 Physicians and Nurses................................................................. 124

SECTION 4. SCREENING........................................................................................128

4.1 HPV Testing................................................................................................ 129



4.2 Cost



4.3 Self-Sampling.............................................................................................144

................................................................................................ 142

SECTION 5. DATA MANAGEMENT AND LINKAGES........................................... 151 SECTION 6. T HERAPEUTIC USE OF VACCINE.....................................................153 SECTION 7. H PV TESTING TECHNOLOGY...........................................................156

7.1 R eviews and Meta-analysis....................................................................... 157



7.2 HPV Screening and Genotyping among

Commercial Methods................................................................................159

7.2.1. Methods for Detection of DNA...................................................159



7.2.2. Methods for Detection of E6 and mRNA or p16........................159



7.3 Novel Technology.......................................................................................168

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Key Findings • HPV 16 and 18 remained the most frequent HPV type identified in cervical cancer (53-84%), in situ cervical cancer (56-73%), and high grade cervical lesions (52–62%). • HPV 18 and 45 were underrepresented in patients with cervical dysplasia development. • Bimodal peaks of cervical HPV infection were evident in younger populations and women over the age of 40. • Current and past smoking behaviors were independent predictors of HPV persistence and risk of developing cervical lesions. • Early onset of sexual activity was an independent risk factor for HPV infection. • Ethnic and racial disparities remain a significant factor among women diagnosed with genital cancers. • HPV 16 and 18 are prevalent in anal precancerous and cancerous lesions. • Anal HPV infections follow a similar pattern of duration and clearance as cervical HPV infection. • HPV 16 is the most common HPV type in posterior naso/oropharyngeal tumors. • Risk factors for head and neck cancers associated with HPV infections included oral sex and number of sex partners. • Non-smokers and non-drinkers who developed oral cancers were six times more likely to have a high risk HPV infection than those who did not develop oral cancer. • A strong association with index and second primary anogenital cancer and oropharyngeal cancers, specifically tonsillar cancer following anal cancer, has been demonstrated. • HPV related oropharyngeal tumors in several studies appeared to frequently metastasize to lymph nodes with prognosis about the same or improved using current treatment regimens. • Studies have confirmed that HIV infection increased HPV infection incidence after controlling for confounders. • HPV 6 and 11 are confirmed as the etiologic factor for most recurrent respiratory papillomatosis. • Lifetime number of sex partners, oral or vaginal sex partners, and current partner HPV infection were significant risk factors for HPV infection in men and couples in new relationships. • HPV 16 was more common and had a longer duration among uncircumcised men. • Clinical trial data have shown moderate impacts of HPV vaccination on non-vaccine oncogenic HPV types 31, 33, 45, 52, and 58.

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• Reductions in genital warts have occurred among vaccinated Australian women under the age of 25. • Factors impeding maximal HPV vaccination uptake have been identified as short notice for vaccine program implementation, negative media, and lack of general practitioner encouragement to eligible females. • HPV vaccination cost effectiveness and modeling studies using current vaccine efficacy data, vaccine costs, and cervical cancer screening rates have not demonstrated value for women over the age of 30 who continue to be screened at least every two years. • Ethnic, cultural, and socio-economic differences impact HPV knowledge and vaccination intention. • Joint decision-making between school aged girls and their parents improved immunization uptake rates. • Cost of vaccination, physician recommendation, and perceived social norms from family and friends impacted HPV vaccination intention and decision-making. • Common characteristics among physicians and nurses related to likelihood to recommend HPV vaccination included individual beliefs, knowledge, support from colleagues, and patient’s insurance coverage. • HPV testing improved disease detection rates in screening and follow up treatment, was more cost-effective, and was a more sensitive test for women over the age of 30 in many studies. • Primary HPV DNA screening with cytology triage in women over the age of 30 was found to be more specific than conventional screening and resulted in decreased rates of colposcopy referral and follow up. • HPV testing offered opportunities to reach high risk populations through HPV selfsampling, bypassing traditional access issues to cervical cancer screening services. • HPV DNA testing technology continued to be evaluated demonstrating clinical utility of Hybrid Capture II and other developing HPV test methods.

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Section 1 Epidemiology and Burden of Disease

SECTION SECTION1:1 EPIDEMIOLOGY - EPIDEMIOLOGY AND ANDBURDEN BURDENOF OFDISEASE DISEASE 1.1 FEMALE GENITAL CANCERS AND DISEASE What have we learned about HPV distribution among different female populations and diseases?

1.1.1 Epidemiology SUMMARY Studies in Europe, China, and United States confirmed HPV 16 and 18 as the most frequent HPV type identified in cervical cancer (53-85%), in situ cervical cancer (56-73%), and high grade cervical lesions (52-62%). HPV 16 occurred more frequently (>75%) and HPV 18 less frequently (75%) and HPV18 less frequently (