Targeting Human Papillomavirus to Reduce the Burden of Cervical, Vulvar and Vaginal Cancer and Pre-Invasive Neoplasia: Establishing the Baseline for Surveillance
Background Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004–2006, prior to the availability of HPV vaccines, in order to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. Methods Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias was obtained from high-quality national population-based registries. A literature review was conducted to define the fraction of these lesions attributable to HPV16/18, i.e., those that could be prevented by HPV vaccination. Results Among the four countries, the age-standardised IR/105 of cervical, vaginal and vulvar cancer ranged from 8.4–13.8, 1.3–3.1 and 0.2–0.6, respectively. The risk for cervical cancer was highest in women aged 30–39, while vulvar and vaginal cancers were most common in women aged 70+. Age-standardised IR/105 of cervical, vulvar and vaginal pre-invasive neoplasia ranged between 138.8？183.2, 2.5？8.8 and 0.5？1.3, respectively. Women aged 20？29 had the highest risk for cervical pre-invasive neoplasia, while vulvar and vaginal pre-invasive neoplasia peaked in women aged 40？49 and 60？69, respectively. Over 50% of the observed 47,820 incident invasive and pre-invasive cancer cases in 2004？2006 can be attributed to HPV16/18. Conclusion In the four countries, vaccination against HPV 16/18 could prevent approximately 8500 cases of gynecological cancer and pre-cancer annually. Population-based cancer and vaccination registries are essential to assess the predicted public health effects of HPV vaccination.
References
[1]
IARC (2007) Human Papillomaviruses. Lyon: WHO Press. 978–92–832–1290–4 978–92–832–1290–4.
[2]
De Vuyst H, Clifford G, Li N, Franceschi S (2009) HPV infection in Europe. Eur J Cancer 45: 2632–2639. doi: 10.1016/j.ejca.2009.07.019
[3]
Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, et al. (2007) Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer 121: 621–632. doi: 10.1002/ijc.22527
[4]
Kjaer SK, Breugelmans G, Munk C, Junge J, Watson M, et al. (2008) Population-based prevalence, type- and age-specific distribution of HPV in women before introduction of an HPV-vaccination program in Denmark. Int J Cancer 123: 1864–1870. doi: 10.1002/ijc.23712
[5]
van de Nieuwenhof HP, van der Avoort IA, de Hullu JA (2008) Review of squamous premalignant vulvar lesions. Crit Rev Oncol Hematol 68: 131–156. doi: 10.1016/j.critrevonc.2008.02.012
[6]
De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S (2009) Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 124: 1626–1636. doi: 10.1002/ijc.24116
[7]
Garland SM, Insinga RP, Sings HL, Haupt RM, Joura EA (2009) Human papillomavirus infections and vulvar disease development. Cancer Epidemiol Biomarkers Prev 18: 1777–1784. doi: 10.1158/1055-9965.epi-09-0067
[8]
Chao FY, Chao A, Huang CC, Hsueh S, Yang JE, et al. (2010) Defining detection threshold and improving analytical proficiency of HPV testing in clinical specimens. Gynecol Oncol 117: 302–307. doi: 10.1016/j.ygyno.2010.02.001
[9]
de Sanjose S, Diaz M, Castellsague X, Clifford G, Bruni L, et al. (2007) Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis 7: 453–459. doi: 10.1016/s1473-3099(07)70158-5
[10]
de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, et al. (2010) Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 11: 1048–1056. doi: 10.1016/s1470-2045(10)70230-8
[11]
Insinga RP, Liaw KL, Johnson LG, Madeleine MM (2008) A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States. Cancer Epidemiol Biomarkers Prev 17: 1611–1622. doi: 10.1158/1055-9965.epi-07-2922
[12]
Smith JS, Backes DM, Hoots BE, Kurman RJ, Pimenta JM (2009) Human Papillomavirus Type-Distribution in Vulvar and Vaginal Cancers and Their Associated Precursors. Obstet Gynecol 113: 917–924. doi: 10.1097/aog.0b013e31819bd6e0
[13]
Ault KA (2007) Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet 369: 1861–1868. doi: 10.1016/s0140-6736(07)60852-6
[14]
Munoz N, Manalastas R Jr, Pitisuttithum P, Tresukosol D, Monsonego J, et al. (2009) Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial. Lancet 373: 1949–1957. doi: 10.1016/s0140-6736(09)60691-7
[15]
Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, et al. (2009) 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. Lancet 374: 301–314. doi: 10.1016/s0140-6736(09)61248-4
[16]
Brotherton J, Gertig D, Chappell G, Rowlands L, Saville M (2011) Catching up with the catch-up: HPV vaccination coverage data for Australian women aged 18–26 years from the National HPV Vaccination Program Register. Commun Dis Intell 35: 197–201.
[17]
Moller B, Fekjaer H, Hakulinen T, Tryggvadottir L, Storm HH, et al. (2002) Prediction of cancer incidence in the Nordic countries up to the year 2020. Eur J Cancer Prev 11 Suppl 1S1–96.
[18]
Larsen IK, Smastuen M, Johannesen TB, Langmark F, Parkin DM, et al. (2009) Data quality at the Cancer Registry of Norway: an overview of comparability, completeness, validity and timeliness. Eur J Cancer 45: 1218–1231. doi: 10.1016/j.ejca.2008.10.037
[19]
Tavassoli F, Devilee P, editors (2003) Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARCPress.
[20]
WHO (1992) The ICD-10 classification of mental and behavioural disorders. Clinical descriptions and diagnostic guidelines. Geneva: World Health Organization. 362 p.
[21]
Bjerregaard B, Larsen OB (2011) The Danish Pathology Register. Scand J Public Health 39: 72–74. doi: 10.1177/1403494810393563
[22]
Sigurdsson K (2010) Cervical cancer: cytological cervical screening in Iceland and implications of HPV vaccines. Cytopathology 21: 213–222. doi: 10.1111/j.1365-2303.2010.00783.x
[23]
Enerly E, Bray F, Mellem C, Hansen BT, Kjolberg G, et al. (2012) Quality assessment of the registration of vulvar and vaginal premalignant lesions at the Cancer Registry of Norway. Acta Oncol 51: 45–50. doi: 10.3109/0284186x.2011.624545
[24]
Andrae B, Kemetli L, Sparen P, Silfverdal L, Strander B, et al. (2008) Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden. J Natl Cancer Inst 100: 622–629. doi: 10.1093/jnci/djn099
[25]
dos Santos Silva I (1999) Cancer Epidemiology: Principles and Methods. Lyon: IARC.
[26]
de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, et al. (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13: 607–615. doi: 10.1016/s1470-2045(12)70137-7
[27]
Miettinen OS (1974) Proportion of disease caused or prevented by a given exposure, trait or intervention. Am J Epidemiol 99: 325–332.
[28]
Eliasen M, Kaer SK, Munk C, Nygard M, Sparen P, et al. (2009) The relationship between age at drinking onset and subsequent binge drinking among women. Eur J Public Health 19: 378–382. doi: 10.1093/eurpub/ckp023
[29]
Hansen BT, Hagerup-Jenssen M, Kjaer SK, Munk C, Tryggvadottir L, et al. (2010) Association between smoking and genital warts: longitudinal analysis. Sex Transm Infect 86: 258–262. doi: 10.1136/sti.2009.038273
[30]
Jensen KE, Munk C, Sparen P, Tryggvadottir L, Liaw KL, et al. (2011) Women’s sexual behavior. Population-based study among 65,000 women from four Nordic countries before introduction of human papillomavirus vaccination. Acta Obstet Gynecol Scand 90: 459–467. doi: 10.1111/j.1600-0412.2010.01066.x
[31]
Olesen TB, Jensen KE, Nygard M, Tryggvadottir L, Sparen P, et al. (2012) Young age at first intercourse and risk-taking behaviours–a study of nearly 65 000 women in four Nordic countries. Eur J Public Health 22: 220–224. doi: 10.1093/eurpub/ckr055
[32]
Kjaer SK, Tran TN, Sparen P, Tryggvadottir L, Munk C, et al. (2007) The burden of genital warts: a study of nearly 70,000 women from the general female population in the 4 Nordic countries. J Infect Dis 196: 1447–1454. doi: 10.1086/522863
[33]
Nygard JF, Nygard M, Skare GB, Thoresen SO (2006) Pap smear screening in women under 30 in the Norwegian Coordinated Cervical Cancer Screening Program, with a comparison of immediate biopsy vs Pap smear triage of moderate dysplasia. Acta Cytol 50: 295–302. doi: 10.1159/000325957
[34]
Sigurdsson K (1999) The Icelandic and Nordic cervical screening programs: trends in incidence and mortality rates through 1995. Acta Obstetricia et Gynecologica Scandinavica 78: 478–485. doi: 10.1034/j.1600-0412.1999.780602.x
[35]
McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, et al. (2008) Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol 9: 425–434. doi: 10.1016/s1470-2045(08)70103-7
[36]
Albrechtsen S, Rasmussen S, Thoresen S, Irgens LM, Iversen OE (2008) Pregnancy outcome in women before and after cervical conisation: population based cohort study. BMJ 337: a1343. doi: 10.1136/bmj.a1343
[37]
Nohr B, Tabor A, Frederiksen K, Kjaer SK (2007) Loop electrosurgical excision of the cervix and the subsequent risk of preterm delivery. Acta Obstet Gynecol Scand 86: 596–603. doi: 10.1080/00016340701279145
[38]
Van de Velde N, Boily MC, Drolet M, Franco EL, Mayrand MH, et al. (2012) Population-level impact of the bivalent, quadrivalent, and nonavalent human papillomavirus vaccines: a model-based analysis. J Natl Cancer Inst 104: 1712–1723. doi: 10.1093/jnci/djs395
[39]
Levy-Bruhl D, Bousquet V, King LA, O’Flanagan D, Bacci S, et al. (2009) The current state of introduction of HPV vaccination into national immunisation schedules in Europe: results of the VENICE 2008 survey. Eur J Cancer 45: 2709–2713. doi: 10.1016/j.ejca.2009.07.023
[40]
Bulkmans NW, Berkhof J, Rozendaal L, van Kemenade FJ, Boeke AJ, et al. (2007) Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet 370: 1764–1772. doi: 10.1016/s0140-6736(07)61450-0
[41]
Naucler P, Ryd W, Tornberg S, Strand A, Wadell G, et al. (2007) Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med 357: 1589–1597. doi: 10.1056/nejmoa073204
[42]
Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, et al. (2010) Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol 11: 249–257. doi: 10.1016/s1470-2045(09)70360-2
[43]
Kjaer SK, Frederiksen K, Munk C, Iftner T (2010) Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst 102: 1478–1488. doi: 10.1093/jnci/djq356
[44]
Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, et al. (2012) American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin 62: 147–172. doi: 10.3322/caac.21139
[45]
Dijkstra MG, Heideman DA, van Kemenade FJ, Hogewoning KJ, Hesselink AT, et al. (2012) Brush-based self-sampling in combination with GP5+/6+-PCR-based hrHPV testing: High concordance with physician-taken cervical scrapes for HPV genotyping and detection of high-grade CIN. J Clin Virol 54: 147–151. doi: 10.1016/j.jcv.2012.02.022
[46]
de Blasio BF, Neilson AR, Klemp M, Skjeldestad FE (2012) Modeling the impact of screening policy and screening compliance on incidence and mortality of cervical cancer in the post-HPV vaccination era. J Public Health (Oxf) 34: 539–547. doi: 10.1093/pubmed/fds040
[47]
van de Nieuwenhof HP, Massuger LF, van der Avoort IA, Bekkers RL, Casparie M, et al. (2009) Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age. Eur J Cancer 45: 851–856. doi: 10.1016/j.ejca.2008.11.037
[48]
Joura EA (2002) Epidemiology, diagnosis and treatment of vulvar intraepithelial neoplasia. Curr Opin Obstet Gynecol 14: 39–43. doi: 10.1097/00001703-200202000-00007
[49]
Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, et al. (2009) Vaccination against HPV-16 Oncoproteins for Vulvar Intraepithelial Neoplasia. N Engl J Med 361: 1838–1847. doi: 10.1056/nejmoa0810097
[50]
Moscicki AB, Ma Y, Farhat S, Jay J, Hanson E, et al. (2013) 27. Natural history of anal HPV in heterosexual women and risks associated with persistence. Sex Health 10: 583. doi: 10.1071/shv10n6ab27
[51]
Ouhoummane N, Steben M, Coutlee F, Vuong T, Forest P, et al.. (2013) Squamous anal cancer: Patient characteristics and HPV type distribution. Cancer Epidemiol.
[52]
Scudellari M (2013) HPV: Sex, cancer and a virus. Nature 503: 330–332. doi: 10.1038/503330a
[53]
Mannweiler S, Sygulla S, Winter E, Regauer S (2013) Two major pathways of penile carcinogenesis: HPV-induced penile cancers overexpress p16ink4a, HPV-negative cancers associated with dermatoses express p53, but lack p16ink4a overexpression. J Am Acad Dermatol 69: 73–81. doi: 10.1016/j.jaad.2012.12.973
[54]
Chirila M, Bolboaca SD (2013) Clinical efficiency of quadrivalent HPV (types 6/11/16/18) vaccine in patients with recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol.
[55]
Read TR, Hocking JS, Chen MY, Donovan B, Bradshaw CS, et al. (2011) The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sex Transm Infect 87: 544–547. doi: 10.1136/sextrans-2011-050234
[56]
Baandrup L, Blomberg M, Dehlendorff C, Sand C, Andersen KK, et al. (2013) Significant decrease in the incidence of genital warts in young danish women after implementation of a national human papillomavirus vaccination program. Sex Transm Dis 40: 130–135. doi: 10.1097/olq.0b013e31827bd66b
[57]
Leval A, Herweijer E, Ploner A, Eloranta S, Fridman Simard J, et al.. (2013) Quadrivalent Human Papillomavirus Vaccine Effectiveness: A Swedish National Cohort Study. J Natl Cancer Inst.
