Abstract
Aim: We used existing data to investigate whether prevalence of HPV16/18 in cervical intraepithelial neoplasia 3 (CIN3) varies by age, in order to determine whether age specific baseline data is required as the prevaccination comparator for type-specific surveillance following HPV vaccination programs. Materials & Methods: We analyzed available Australian HPV typing data from 317 cervical smears from women with concurrent CIN3 on biopsy and conducted a review and analysis of the international literature. Results: Among 317 women with CIN3, HPV16 was detected in 70% of those 16–25 years old, 59% of 26–35-year-olds and 48% of >36-year-olds (p = 0.025). This association took the form of a trend with decreasing HPV16 prevalence with increasing age (p = 0.007). That HPV16 is commoner in younger women with high-grade cervical lesions was consistent with all but one study of 18 identified in the literature. Conclusion: In screened populations, younger women with CIN3 are more likely to have HPV16 detected. To make valid pre- and post-vaccination comparisons, surveillance specimens for HPV typing should be both age stratified and lesion specific.
Papers of special note have been highlighted as: ▪ of interest
References
- 1 Clifford G, Smith J, Aguado T, Franceschi S. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br. J. Cancer89,101–105 (2003).
- 2 Clifford G, Rana R, Franceschi S, Smith J, Gough G, Pimenta J. Human papillomavirus genotype distribution in low-grade cervical lesions: comparison by geographic region and with cervical cancer. Cancer Epidemiol. Biomarkers Prev.14,1157–1164 (2005).
- 3 Smith JS, Lindsay L, Hoots B et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int. J. Cancer121,621–632 (2007).▪ Meta-analysis of HPV types detected in 14,595 cervical cancer specimens and 7094 high-grade cervical lesions from around the world.
- 4 Brestovac B, Harnett G, Smith D, Frost F, Shellam G. Human papillomavirus genotypes and their association with cervical neoplasia in a cohort of western Australian women. J. Med. Virol.76,106–110 (2005).
- 5 Stevens M, Tabrizi S, Quinn M, Garland S. Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Melbourne, Australia. Int. J. Cancer16,1017–1024 (2006).▪ Shows that the two most prevalent cervical cancer-associated genotypes in Australia (HPV16 and 18) parallel those described internationally.
- 6 Stevens MP, Garland SM, Tan JH, Quinn MA, Petersen RW, Tabrizi SN. HPV genotype prevalence in women with abnormal Pap smears in Melbourne, Australia. J. Med. Virol.81,1283–1291 (2009).
- 7 Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia grade 2. Obstet. Gynecol. Surv.64,306–308 (2009).
- 8 Franceschi S, Clifford G. Re: a study of the impact of adding HPV types to cervical cancer screening and triage tests [letter]. J. Natl Cancer Inst.97(12),938–939 (2005).
- 9 Wentzensen N, Schiffman M, Dunn ST et al. Grading the severity of cervical neoplasia based on combined histopathology, cytopathology, and HPV genotype distribution among 1700 women referred to colposcopy in Oklahoma. Int. J. Cancer124,964–969 (2009).
- 10 De Vuyst H, Clifford G, Li N, Franceschi S. HPV infection in Europe. Eur. J. Cancer45,2632–2639 (2009).
- 11 Sargent A, Bailey A, Almonte M et al. Prevalence of type-specific HPV infection by age and grade of cervical cytology. data from the ARTISTIC trial. Br. J. Cancer98,1704–1709 (2008).
- 12 Rodriguez AC, Schiffman M, Herrero R et al. Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J. Natl Cancer Inst.100,513–517 (2008).
- 13 Wheeler CM, Hunt WC, Joste NE et al. Human papillomavirus genotype distributions. implications for vaccination and cancer screening in the United States. J. Natl Cancer Inst.101,475–487 (2009).
- 14 Chen W, Zhang X, Molijn A et al. Human papillomavirus type-distribution in cervical cancer in China: the importance of HPV 16 and 18. Cancer Causes Control20,1705–1713 (2009).
- 15 Sigurdsson K, Taddeo FJ, Benediktsdottir KR et al. HPV genotypes in CIN2–3 lesions and cervical cancer: a population based study. Int. J. Cancer121,2682–2687 (2007).
- 16 Stevens MP, Garland SM, Rudland E, Tan J, Quinn MA, Tabrizi SN. Comparison of the Digene Hybrid Capture 2 assay and Roche Amplicor and linear array human papillomavirus (HPV) tests in detecting high-risk HPV genotypes in specimens from women with previous abnormal pap smear results. J. Clin. Microbiol.45(7),2130–2137 (2007).
- 17 Cuschieri KS, Cubie HA, Whitley MW et al. Multiple high-risk HPV infections are common in cervical neoplasia and young women in a cervical screening population. J. Clin. Pathol.57,68–72 (2004).
- 18 Kjaer SK, Breugelmans G, Munk C, Junge J, Watson M, Iftner T. Population-based prevalence, type and age-specific distribution of HPV in women before introduction of an HPV vaccination program in Denmark. Int. J. Cancer123,1864–1870 (2008).
- 19 Howell-Jones R, Bailey A, Beddows S et al. Multi-site study of HPV type-specific prevalence in women with cervical cancer, intraepithelial neoplasia and normal cytology, in England. Br. J. Cancer103,209–216 (2010).▪ Comprehensive prevaccination baseline study from England.
- 20 Castle PE, Schiffman M, Wheeler CE, Wentzensen N, Gravitt PE. Human papillomavirus genotypes in cervical intraepithelial neoplasia. Cancer Epidemiol. Biomarkers. Prev.19,1675–1681 (2010).
- 21 Masumoto N, Fujii T, Ishikawa M et al. Dominant human papillomavirus 16 infection in cervical neoplasia in young Japanese women: study of 881 outpatients. Gynecol. Oncol.94(2),509–514 (2004).
- 22 Carozzi FM, Tornesello ML, Burroni E et al. HPV Prevalence Italian Working Group. Prevalence of human papillomavirus types in high-grade cervical intraepithelial neoplasia and cancer in Italy. Cancer Epidemiol. Biomarkers Prev.19(9),2389–2400 (2010).
- 23 Castle PE, Shaber R, LaMere BJ et al. Human papillomavirus (HPV) genotypes in women with cervical precancer and cancer at Kaiser Permanente Northern California. Cancer Epidemiol. Biomarkers Prev.20(5),946–953 (2011).
- 24 Gargano JW, Nisenbaum R, Lee DR et al. Age-group differences in human papillomavirus types and cofactors for cervical intraepithelial neoplasia 3 among women referred to colposcopy. Cancer Epidemiol. Biomarkers Prev. doi:10.1158/1055-9965 (2011) (Epub ahead of print).
- 25 Baandrup L, Munk C, Andersen KK, Junge J, Iftner T, Kjær SK. HPV16 is associated with younger age in women with cervical intraepithelial neoplasia grade 2 and 3. Gynecol. Oncol. doi:10.1016/j.ygyno.2011.10.020 (2011) (Epub ahead of print).
- 26 Porras C, Rodriguez AC, Hildesheim A et al. Human papillomavirus types by age in cervical cancer precursors: predominance of human papillomavirus 16 in young women. Cancer Epidemiol. Biomarkers Prev.18(3),863–865 (2009).
- 27 Ivansson EL, Gustavsson IM, Wilander E, Magnusson PKE, Gyllensten UB. Temporal trends over 3 decades and intrafamilial clustering of HPV types in Swedish patients with cervical cancer in situ. Int. J. Cancer125,2930–2935 (2009).
- 28 Evans MF, Adamson CS, Papillo JL, St John TL, Leiman G, Cooper K. Distribution of human papillomavirus types in Thin Prep Papanicolau tests classified according to the Bethesda 2001 terminology and correlations with patient age and biopsy outcomes. Cancer106,1054–1064 (2006).
- 29 Chao A, Jao MS, Huang CC et al. Human papillomavirus genotype in cervical intraepithelial neoplasia grade 2 and 3 of Taiwanese women. Int. J. Cancer128(3),653–659 (2010).
- 30 Onuki M, Onuki M, Matsumoto K et al. Human papillomavirus infections among Japanese women. Age-related prevalence and type-specific risk for cervical cancer. Cancer Sci.100,1312–1316 (2009).
- 31 Sukasem C, Pairoj W, Saekang N et al. Molecular epidemiology of human papillomavirus genotype in women with high-grade squamous intraepithelial lesion and cervical cancer: will a quadrivalent vaccine be necessary in Thailand? J. Med. Virol.83(1),119–126 (2011).
- 32 Garland SM, Brotherton JML, Condon JR et al. Human papillomavirus prevalence amongst indigenous and non-indigenous Australian women prior to a national HPV vaccination program. BMC Med.9(1),104 (2011).
- 33 Khan MJ, Castle PE, Lorincz AT et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J. Natl Cancer Inst.97(14),1072–1079 (2005).
- 34 Kjær SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J. Natl Cancer Inst.102(19),1478–1488 (2010).
- 35 Brotherton JML. How much cervical cancer in Australia is vaccine preventable? A meta-analysis. Vaccine26,250–256 (2008).
- 36 Lehtinen M, Paavonen J, Wheeler CM et al. for the HPV PATRICIA Study Group. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. doi:10.1016/S1470-2045(11)70286-8 (2011) (Epub ahead of print).
- 37 Muñoz N, Kjaer SK, Sigurdsson K et al. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women. J. Natl Cancer Inst.102(5),325–339 (2010).
- 38 Stoler M. It is more complicated than you think: doctor, which HPV type caused that lesion? HPV Today, 4–6 February (2010).
- 39 Quint W, Jenkins D, Molijn A et al. One virus one lesion – individual components of CIN lesions contain a specific HPV type. J. Pathol.30, doi:10.1002/path.3970 (2011) (Epub ahead of print).
- 40 Espina V, Heiby M, Pierobon M, Liotta LA. Laser capture microdissection technology. Expert Rev. Mol. Diagn.7(5),647–657 (2007).
- 41 Paavonen J, Naud P, Salmerón J et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet374,301–314 (2009).
- 101 WHO/ICO Information Centre on human papillomavirus and cervical cancer. Data query. http://apps.who.int/hpvcentre/statistics/dynamic/ico/SummaryReportsSelect.cfm (Accessed 3 May 2010).
- 102 Australian Institute of Health and Welfare. Cervical Screening in Australia 2006–2007. Cancer series no. 47. Cat. no. CAN43. Canberra: AIHW (2009). www.aihw.gov.au/publication-detail/?id=6442468228