Prophylactic HPV vaccines

Infection with human papillomavirus (HPV), in particular HPV 16 and HPV 18, is the main cause of cervical cancer. Two prophylactic vaccines against types 6, 11, 16 and 18 have shown great promise in clinical trials, with recent results demonstrating100% efficacy against persistent HPV infection and development of CIN up to five years of follow-up. One of these (Gardasil, recently licensed) contains all four HPV types, offering protection against genital warts (types 6 and 11) as well as cervical cancer. The other (Cervarix) contains types 16 and 18, targeting cervical cancer alone. Recent data suggest a degree of cross-protection, against types 31 and 45; this could significantly increase the level of protection afforded by the vaccines. It is envisaged that girls between 11 and 12 will be the target, and this is what has been recommended in the United States. There is still debate about the issue of vaccinating boys. A fundamental issue is the lack of education of both the public and health professionals about HPV. In theory, an HPV vaccine could prevent almost all cervical cancer, eventually removing the need for cervical smears. However, there is at least one whole generation of women for whom the vaccine will come too late, and who will continue to require screening.

Human papillomavirus; Cervical cancer; Vaccines

[1] Ferlay J., Bray P., Pizani P., Parkin D.M.: "Cancer incidence, mortality and prevalence worldwide". IARC Cancer, Base No. 5, version 2.0 Lyon, France, IARC Press, 2004.

[2] Peto J., Gilham C., Fletcher O. & Matthews F.E.:'The cervical cancer epidemic that screening has prevented in the UK". Lancet, 2004, 364 (9430), 249.

[3] French D.P., Maissi E., Marteau T.M.: "Psychological costs of inadequate cervical smear test results". Br. J. Cancer, 2004, 91, 1887.

[4] Lerman C., Miller S.M., Scarborough R., Hanjani P., Nolte S., Smith D.: "Adverse psychologic consequences of positive cytologic cervical screening". Am. 1. Obstet. Gynecol., 1991, 165,658.

[5] Cohen J.: "High Hopes and Dilemmas for a cervical cancer vaccine". Science, 2005, 308, 618.

[6] Wolstenholme J.L., Whynes D.K.: "Stage-specific treatment costs for cervical cancer in the United Kingdom". Eur. J. Cancer, 1998, 34, 1889.

[7] Jacob M., Broekhuizen F.F., Castro W., Sellors J.: "Experience using cryotherapy for treatment of cervical precancerous lesions in low-resource settings". Int. J. Gynaecol. Ohstet., 2005, 89(、uppl. 2). S13.

[8] J Walboomers J.M., Jacobs M.V., Manos M.M., Bosch F.X., Kummer J.A., Shah K.V. et al.: "Human papillomavirus is a necesAary cause of invasive cervical cancer worldwide". J. Pathol., 1999, 189, 12.

[9] Collins Y., Einstein M.H., Gostout B., Herzog T.J., Massad L.S., Rader J.S., Wright J.: "Cervical cancer prevention in the era of prophylactic vaccines: A preview for gynecologic oncologists". Gynecologic Oncology, 2006, 102, 552.

[10] Parkin D.M., Bray F.: "The burden of HPV - related cancers". Vaccine, 2006, 24S3, S3/11.

[ 11] Koutsky L.: "Epidemiology of Genital Human Papillomaviru、Infection". Am. J. Med., 1997, 102, 3.

[12] Lacey C., Lowndes C.M., Shah K.V.: "Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease". Vaccine, 2006, 24S3, S3/35.

[13] Brown R.E., Breugelmans J.G., Theodoratou D., Benard S.: "Costs of detection and treatment of cervical cancer, cervical dysplasia and genital warts in the UK". Curr. Med. Res. Opin., 2006, 22, 663.

[14] Stanley M.: "Immune responses to human papillomavirus". Vaccine, 2006, 24SI, Sl/16.

[15] Harper D.M., Franco E.L., Wheeler C., Ferris D.G., Jenkins D., Schuind A. et al.: "Efficacy of a bivalent LI virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial". Lancet, 2004, 364, 1757.

[16] Villa L.L., Costa R.R., Petta C.A., Andrade R.P., Ault K.A., Giuliano A.R. et al.: "Prophylactic quadrivalent human papillomavirus (types 6, 11, 16 and 18) LI virus-like particle vaccine in young women: a randomised double-blind placebo controlled multicentre phase II efficacy trial". Lancet Oncol., 2005, 6, 271.

[17] Boland G., Beran J., Lievens M. et al.: "Safety and immunogenicity profile of an experimental hepatitis B vaccine adjuvanted with AS04". Vaccine, 2004, 23, 316.

[18] Dubin G.: "HPV vaccine Adolescent Study Investigators Network". Enhanced immunogenicity of a candidate human papillomavirus (HPV) 16/18 LI virus like particle (VLP) vaccine with novel AS04 adjuvant in pre-teens/adolescents (abstract LB2-8). Presented at: the 45th Inter­science Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Washington DC, December 16-19, 2005.

[19] Harper D.M., Franco E.L., Wheeler C.M. et al.: "Sustained efficacy up to 4.5 years of a bivalent LI virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial". Lancet, 2006, 367, 1247.

[20] Villa L.L., Costa R.L., Petta C.A., Andrade R.P., Paavonen J., Iversen O.E. et al.: "High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 LI virus-like particle vaccine through 5 years of follow-up". Br. J. Cancer, 2006, 95, 1459.

[21] Siddiqui M.A.A., Perry C.M.: "Human papillomavirus quadrivalent (types 6, 11, 16, 18) recombinant vaccine (Gardasil)". Drugs, 2006, 66, 1263.

[22] Schwarz T.F.: "ASCO Proceedings". J. Clin. Oncol., 2006, 24 (suppl.), 1008.

[23] Giannini S.L., Hanon E., Moris P., Van Mechelen M., Morel S., Dessy F., Fourneau M.A., Colau B., Suzich J., Losonksy G., Martin M.T., Dubin G., Wettendorff M.A.: "Enhanced humoral and memory B cellular immunity using HPV16/18 LI VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only". Vaccine, 2006, 24, 5937.

[24] Smith J.F., Brownlow M.K., Brown M.J., Esser M.T., Ruiz W., Brown D.R.: "Gardasil antibodies cross neutralize pseudovirion infection of vaccine-related HPV types". Presented at the International Papillomavirus Conference, 2006 (PL).

[25] Stanley M., Lowy D.R., Frazer I.: "Prophylactic HPV vaccines: underlying mechanisms". 2006, 24S3, S3/106.

[26] Clifford G.M., Gallus S., Herrero R. et al.: "Worldwide distribution of human papillomavirus types in cytologically normal women in the Inter­national Agency for Research on Cancer HPV prevalence surveys: a pooled analysis". Lancet, 2005, 366, 991.

[27] Miura S., Matsumoto K., Oki A., Satoh T., Tsunoda H., Yasugi T. et al.: "Do we need a different strategy for HPV screening and vaccination in East Asia?". Int. J. Cancer, 2006, 119, 2713.

[28] Rosenthal S.L., Stanberry L.R.: "Parental acceptability of vaccines for sexually transmitted infections". Archives of Paediatrics & Adolescent Medicine, 2005, 159, 190.

[29] Lazcano-Ponce E., Rivera L., Arillo-Santillan E., Salmeron J., Hernandez-Avila M., Munoz N.: "Acceptability of a human papillomavirus (HPV) trial vaccine among mothers of adolescents in Cuernavaca, Mexico". Archives of Medical Research, 2001, 32, 243.

[30] Kahn J.A., Rosenthal S.L., Hamann T., Bernstein D.I.: "Attitudes about human papillomavirus vaccine in young women". Int. J. STD AIDS, 2003, 14, 300.

[31] Zimet G.D., Mays R.M., Sturm L.A., Ravert A., Perkins S.M., Juliar B.E.: "Parental attitudes about sexually transmitted infection vaccination for their adolescent children". Arch. Pediatr. Adolesc. Med., 2005, 159, 132.

[32] Slomovitz B.M., Sun C.C., Frumovitz M., Soliman P.T., Schmeler K.M., Pearson H.C., Berenson A., Ramirez P.T., Lu K.H., Bodurka D.C.: "Are women ready for the HPV vaccine?". Gynecologic Oncology, 2006, 103, 151.

[33] Brabin L., Roberts S.A., Farzaneh F., Kitchener H.C.: "Future acceptance of adolescent human papillomavirus vaccination: a survey of parental attitudes". Vaccine, 2006, 24, 3087.

[34] Waller J., Marlow L.A.V., Wardle J.: "Mothers'Attitudes towards Preventing Cervical Cancer through Human Papillomavirus Vaccination: A Qualitative Study". Cancer Epidemiol. Biomarkers Prev., 2006, 15 (7), 1257.

[35] Joint Committee on Vaccination and Immunisation. In Minutes of meeting 22/09/06. http://www.advisorybodies.doh.gov.uk/jcvi/ mins-hpv-220906.htrn.

[36] Bottiger M., Forsgren M.: "Twenty years'experience of rubella vaccination in Sweden: 10 years of selective vaccination (of 12-year-old girls and of women postpartum) and 13 years of a general two-dose vaccination". Vaccine, 1997, 15, 1538.

[37] Hughes J.P., Garnett G.P., Koutsky L.: "The theoretical population-level impact of a prophylactic human papilloma virus vaccine". Epidemi­ology, 2002, 13, 631.

[38] Garnett G.P.: "Role of herd immunity in determining the effect of vaccines against sexually transmitted disease". J. Infect. Dis., 2005, Feb 1, 191 (suppl. ]), S97.

[39] Kim J.J., Folse H., Murray M., Goldie S.J.: "Should men be included in a vaccination program against human papillomavirusinfection". Pre-sented at IPV, 2006, PS I.

[40] Martin F., Bower M.: "Anal intraepithelial neoplasia in HIV positive people". Sex Transm. Inf, 2001, 77, 327.

[41] Kane M.A., Sherris J., Coursaget P., Aguado T., Cutts F.: "HPV vaccine use in the developing world". Vaccine, 2006, 24S3, S3/132.

[42] Cuschieri K.S., Horne A.W., Szarewski A., Cubie H.A.: "Public awareness of human papillomavirus". J. Med. Screen, 2006, 13, 201.

[43] Franco E.L., Villa L.L., Sobrinho J.P., Prado J.M., Rousseau M.-C., Desy M. et al.: "Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from ahigh risk area for cervical cancer". J. Infect. Dis., 1999, 180, 1415.

[44] Munoz N., Mendez F., Posso H., Molano M., van den Brule A.J., Ronderos M. et al.: "Incidence, duration, and determinants of cervical human papillomavirus infection in a cohort of Colombian women with normal cytological results". J. Infect. Dis., 2004, 190, 2077.

[45] Sellors J.W., Karwalajtys T.L., Kaczorowski J., Mahony J.B., Lytwyn A., Chong S. et al.: "Incidence, clearance and predictors ofhuman pap止 lomavirus infection in women". C.M.A.J., 2003, 168, 421.

[46] Grainge M.J., Seth R., Guo L., Neal K.R., Coupland C., Vryenhoef P. et al.: "Cervical human papillomavirus screening among older women". Emerg. Infect. Dis., 2005, 11, 1680.

[47] Schiller J.T., Nardelli-Haefliger D.: "Second generation HPV vaccines to prevent cervical cancer". Vaccine, 2006, 24 (S3), S3/147.