Burden of HPV Incidence in Nunavut

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26th International Papillomavirus Conference: Satellite Symposium
Enhancing HPV Prevention among Indigenous Populations: International Perspectives on Health and Well-Being
Montreal, Quebec
July 5, 2010

Panel 1 , Researching the Burden of HPV Disease, Immunization, and Cervical Screening among Indigenous Populations.

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  • Nunavut’s 30,000 inhabitants live in 28 communities widely scattered across 2 million square kilometres. All communities are accessible by air and by sea. The Inuit have occupied the region for thousands of years and form almost 85 percent of the current population. Their languages, Inuktitut and Innuinaqtun are spoken by 80 per cent of the population. Nunavut's society is the youngest in Canada, with half the population under 21. Nunavut was established as a new Territory in 1999, as a result of a land claim agreement between the Inuit of the North West Territories and the Government of Canada. Among Canada’s 10 Provinces and 3 Territories, Nunavut is the only jurisdiction whose population is overwhelmingly aboriginal. (85% Inuit)
  • There are limited data regarding the prevalence and type distribution of human papillomavirus (HPV) and its relationship to cervical cancer and its precursors in Nunavut. preliminary data from previous unpublished research suggested that the predominant circulating HPV types in the territory of Nunavut may differ from those found in studies in southern regions of Canada and in other countries. Following the advent of HPV vaccines, a key public health question has been whether immunization programs will be effective in reducing the prevalence of HPV 16 and HPV 18 which are significantly associated with cervical cancer; a secondary question concerns whether any changes in the types of HPV most associated with cervical cancer will change as a result of immunization against HPV 16 and 18.
  • Alberto Severini’s notes on lab methods: Method developed at NML Genotyping of 45 mucosal HPV types, both high and low risk Amplification by nested PCR (PGMY primers and GP5+/GP6+) Detection by Luminex technology Compares favourably to the Roche LinearArray genotyping method More types detected more positive samples detected No cross-hybridization of HPV 52 Less sensitive for multiple infections with many types
  • For prevalence calculations, where more than one specimen per individual existed, a random selection was performed to create a data subset that contained one set of results for each individual.   HPV prevalence and cytological results were age standardized to the 2006 Nunavut population based on the 2006 Canadian Census for comparisons between Inuit and non-Aboriginal females. The association between Pap result and HPV type was calculated using odds ratios (OR) and 95% confidence intervals (CI) using all results for each participant, excluding those with a non-diagnostic Pap result. The outcomes of particular interest were cytological results most likely to lead to invasive cervical cancer. atypical squamous cells, unable to exclude high-grade intraepithelial lesion (ASC-H), high-grade intraepithelial lesion (HSIL), and squamous cell carcinoma results were combined to create a category of “high grade cervical lesions.” All other cervical cytology findings were combined as non-high-grade cervical cytology for Odds Ratio calculations.  
  • A final dataset of 4,683 records with both valid cytology and HPV results was created, representing 4,043 individual females. Of those with known age (N = 3,877), the median age was 30 years (range 13 to 77) and 32.8% were under the age of 25. Of those with known ethnicity (N = 4033), 3596 were identified as Inuit (89.2%), 17 First Nations (0.4%), and 420 non-Aboriginal (10.4%). There were significant differences in the median age of Inuit and non-Aboriginal women (29 vs. 35 years, respectively; p<0.001).
  • HPV 81 had the highest prevalence of all the low risk types at 1.6%. The prevalence of low risk HPV types 6 and 11 were 1.3% and 0.3%, respectively.
  • To compare HPV and Pap outcomes in Inuit and non-Aboriginal women, results were age-standardized to the 2006 Nunavut population due to differences in the age structure of the populations. Statistically significant differences are highlighted in blue. Type-specific comparisons between groups were limited by the small number of non-Aboriginal women in the Nunavut population Abnormal Pap result: Includes atypical cells of undetermined significance (ASCUS), atypical glandular cells, low grade squamous intraepithelial lesion (LSIL), atypical squamous cells, unable to exclude high-grade intraepithelial lesion (ASC-H), high-grade intraepithelial lesion (HSIL), and squamous cell carcinoma High grade lesion: Includes atypical squamous cells, unable to exclude high-grade intraepithelial lesion (ASC-H), high-grade intraepithelial lesion (HSIL), and squamous cell carcinoma
  • High grade lesion: Includes atypical squamous cells, unable to exclude high-grade intraepithelial lesion (ASC-H), high-grade intraepithelial lesion (HSIL), and squamous cell carcinoma All valid (i.e. diagnostic) test results were used to examine the association between HR HPV type and cervical cytological outcome (Pap result). A high-grade abnormal Pap result with a classification of ASC-H, HSIL, or squamous cell carcinoma was the outcome of interest. HPV 31 had one of the lowest ORs associated with high grade lesions, despite its relatively high prevalence in this population
  • Burden of HPV Incidence in Nunavut

    1. 1. Burden of HPV Disease in Nunavut Isaac Sobol 1 , Stephanie Totten 2 , Alberto Severini 2 , Vanessa Goleski 2 , Gordon Johnson 3 , Gayatri Jayaraman 2 , Yang Mao 2 , Tom Wong 2 1. Nunavut Department of Health and Social Services, 2. Public Health Agency of Canada, 3. Dynalife Dx Enhancing HPV Prevention among Indigenous Populations: International Perspectives on Health and Well-Being Symposium Montreal, Canada July 5, 2010
    2. 2.
    3. 3.
    4. 4. Nunavut Facts <ul><li>Established 1999 </li></ul><ul><li>Population 30,000 </li></ul><ul><li>85% Inuit </li></ul><ul><li>50% under age 21 </li></ul><ul><li>Inuktitut and Innuinaqtun spoken by 80% of the population </li></ul><ul><li>25 communities-- only accessible by air or sea </li></ul>
    5. 5. HPV and related disease in Nunavut <ul><li>Cervical cancer incidence decreased between 1994 and 2000 in Nunavut </li></ul><ul><li>2005 Pap screening rate of 79.3% (screened within the last 3 years) </li></ul><ul><li>1999 study of 19 communities, representing 80% of NU population (Healy et al, 2001) found a 26% prevalence of high risk HPV and 6.9% SIL </li></ul><ul><li>Publicly funded, school-based vaccination program initiated March 2010 (grade 6 girls) </li></ul>
    6. 6. HPV Surveillance in Nunavut <ul><li>Initiated in 2008 in collaboration with the Public Health Agency of Canada </li></ul><ul><li>Objectives: </li></ul><ul><ul><li>Provide evidence for decision-making around the HPV vaccine in Nunavut </li></ul></ul><ul><ul><li>Examine differences in HPV prevalence in Inuit and non-Inuit women </li></ul></ul><ul><ul><li>Contribute to national baseline prevalence of HPV prevalence </li></ul></ul>
    7. 7. Surveillance Methods <ul><li>Routine Pap screening at all Nunavut community health clinics January 2008 to March 2009 </li></ul><ul><li>Cytology performed at Dynalife Dx, Edmonton (usual practice) </li></ul><ul><li>Leftover liquid-based cytology specimen sent to National Microbiology Laboratory for HPV typing </li></ul><ul><li>Non-nominal results linked by unique ID </li></ul>
    8. 8. Analysis <ul><li>Prevalence of HPV types and Pap results in all Nunavut women </li></ul><ul><li>Comparison of age-standardized rates between Inuit and non-Aboriginal women </li></ul><ul><li>Association between high risk HPV type and high grade cervical lesion in Inuit women (OR, 95% confidence interval) </li></ul><ul><ul><li>High risk types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82 (Munoz et al, 2003) </li></ul></ul><ul><ul><li>High grade lesion includes Bethesda categories ASC-H, HSIL, squamous cell carcinoma </li></ul></ul>
    9. 9. HPV prevalence in Nunavut women (N = 4,043) HPV Result N % Any HPV 1207 29.9 Multiple types of HPV 385 9.5 Any high risk HPV type 893 22.1 Multiple high risk types 197 4.9
    10. 10. Prevalence of most common high risk HPV types in Nunavut women (N = 4,043) HPV type N % HPV 16 259 6.4 HPV 31 125 3.1 HPV 59 92 2.3 HPV 58 82 2 HPV 45 77 1.9 HPV 66 75 1.9 HPV 39 71 1.8 HPV 51 69 1.7 HPV 18 57 1.4 HPV 33 49 1.2
    11. 11. Prevalence of Pap outcomes in Nunavut women (N = 4,043) Pap Result N % Non-Diagnostic 12 0.3 Benign/Negative 3747 92.7 ASC-US 125 3.1 Atypical Glandular Cells, NOS 1 0 LSIL 104 2.6 ASC-H 25 0.6 HSIL 28 0.7 Squamous cell carcinoma, NOS 1 0
    12. 12. Age-standardized prevalence of HPV and Pap outcomes in Inuit and non-Aboriginal women (N = 3,854) Positive for: Non-Aboriginal (N=401) Inuit (N=3,453) N Age-standardized % (95% CI) N Age-standardized % (95% CI) Abnormal Pap 16 3.1 (1.5, 4.7) 255 6.7 (5.0, 8.3) High grade lesion <5 0.3 (0.0, 0.7) 48 1.0 (0.7, 1.3) Any HPV type 86 18.2 (14.3, 22.2) 1,070 28.7 (25.9, 31.6) 2+ HPV types 21 4.8 (2.6, 6.9) 351 9.1 (7.3, 10.8) High risk HPV 61 12.3 (9.3, 15.4) 795 21.3 (18.6, 24.0) 2+ high risk HPV 9 1.8 (0.5, 3.1) 180 4.7 (3.4, 5.9) HPV16 and/or 18 23 4.5 (2.6, 6.5) 267 7.8 (5.6, 9.5) HPV 16 18 3.8 (1.9, 5.6) 226 6.1 (4.4, 7.7) HPV 31 <5 0.5 (0.0, 1.0) 115 2.4 (2.0, 2.9) HPV 58 <5 0.5 (0.0, 1.0) 75 2.9 (1.3, 4.4) HPV 59 5 1.1 (0.0, 2.2) 86 1.9 (1.5, 2.4) Low risk HPV 23 4.9 (2.8, 7.0) 287 7.3 (6.0, 8.7)
    13. 13. Odds of high grade cervical lesion associated with type-specific HPV infection in Inuit women (N = 4196) HPV type Normal result or low grade lesion (N=4122) High grade lesion (N=74) N % N % OR (95% CI) HPV16 272 6.6 35 47.3 12.7 (7.9, 20.4) HPV18 62 1.5 6 8.1 5.8 (2.4, 13.8) HPV26 1 0.0 1 1.4 56.5 (3.5, 911.3) HPV31 151 3.7 6 8.1 2.3 (1.0, 5.4) HPV33 53 1.3 3 4.1 3.2 (1.0, 10.6) HPV35 35 0.8 5 6.8 8.5 (3.2, 22.3) HPV39 72 1.7 3 4.1 2.4 (0.7, 7.7) HPV45 88 2.1 8 10.8 5.6 (2.6, 11.9) HPV52 53 1.3 2 2.7 2.1 (0.5, 8.9) HPV56 45 1.1 4 5.4 5.2 (1.8, 14.8) HPV58 88 2.1 6 8.1 4.0 (1.7, 9.6) HPV59 104 2.5 3 4.1 1.6 (0.5, 5.3) HPV66 86 2.1 1 1.4 0.6 (0.1, 4.7) HPV73 20 0.5 1 1.4 2.8 (0.4, 21.2)
    14. 14. Summary <ul><li>High rates of HPV in Nunavut </li></ul><ul><li>Inuit women have higher rates of some, but not all HPV types and higher rates of HPV overall than non-Aboriginal women </li></ul><ul><ul><li>Particularly in younger age groups </li></ul></ul><ul><ul><li>Rates of high grade cervical lesions are not significantly different between groups </li></ul></ul><ul><li>Prevalence of HPV 31 is higher than in studies done in other parts of Canada, but its significance to the development of cervical cancer is uncertain </li></ul>
    15. 15. Conclusions <ul><li>Rates of HPV types contained in the quadrivalent vaccine provided evidence for the introduction of a territorial immunization program </li></ul><ul><li>Reasons for higher rates of some HPV types in Inuit women require investigation </li></ul><ul><li>Further surveillance will increase statistical power to examine the risk of high grade lesions due to HPV infection in Inuit women </li></ul>
    16. 16. Acknowledgement <ul><li>The authors gratefully acknowledge the participation of the women of Nunavut in this important surveillance initiative. </li></ul>

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