Human Papillomavirus Vaccination. Current Indications and Future Directions.

Obstetrics and Gynecology Clinics of North America

Volumn 40, Issue 2, 2013, Pages 177-197

  Gattoc, Leda ^a   Nair, Navya ^a   Ault, Kevin ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cervical dysplasia; Genital warts; HPV cervical cancer; Vaccination; Vulvar dysplasia

Indexed keywords

DENDRITIC CELL VACCINE; DNA VACCINE; MEDI 517; PLACEBO; UNCLASSIFIED DRUG; V 503; V 504; VGX 3100; WART VIRUS VACCINE;

ANTIBODY RESPONSE; ANUS CANCER; ANUS CARCINOMA; CANCER INCIDENCE; CONDYLOMA ACUMINATUM; CROSS PROTECTION; DOSAGE SCHEDULE COMPARISON; DRUG COST; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG INDICATION; DRUG SAFETY; HEAD AND NECK CANCER; HEALTH INSURANCE; HUMAN; HUMAN PAPILLOMAVIRUS TYPE 11; HUMAN PAPILLOMAVIRUS TYPE 16; HUMAN PAPILLOMAVIRUS TYPE 18; HUMAN PAPILLOMAVIRUS TYPE 6; IMMUNOGENICITY; OROPHARYNX CANCER; PAPILLOMAVIRUS INFECTION; PREVALENCE; PRIORITY JOURNAL; REVIEW; RISK REDUCTION; UTERINE CERVIX CANCER; UTERINE CERVIX CARCINOMA; UTERINE CERVIX CARCINOMA IN SITU; UTERINE CERVIX DYSPLASIA; VACCINATION; VAGINA CANCER; VAGINAL INTRAEPITHELIAL NEOPLASIA; VULVA CANCER;

ADOLESCENT; ADULT; ANUS NEOPLASMS; CHILD; CONDYLOMATA ACUMINATA; FEMALE; HUMAN PAPILLOMAVIRUS 16; HUMAN PAPILLOMAVIRUS 18; HUMANS; MALE; MASS SCREENING; MIDDLE AGED; OROPHARYNGEAL NEOPLASMS; PAPILLOMAVIRUS INFECTIONS; PAPILLOMAVIRUS VACCINES; PRACTICE GUIDELINES AS TOPIC; RISK FACTORS; SEXUALLY TRANSMITTED DISEASES; UTERINE CERVICAL DYSPLASIA; UTERINE CERVICAL NEOPLASMS; VAGINAL SMEARS; VULVAR NEOPLASMS; YOUNG ADULT;

EID: 84878654468     PISSN: 08898545     EISSN: 15580474     Source Type: Journal    
DOI: 10.1016/j.ogc.2013.03.007     Document Type: Review

References (99)

1. Weinstock H., Berman S., Cates W. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex Reprod Health 2004, 36(1):6-10.
2. Hariri S., Unger E.R., Sternberg M., et al. Prevalence of genital human papillomavirus among females in the United States, the National Health And Nutrition Examination Survey, 2003-2006. J Infect Dis 2011, 204(4):566-573.
3. Bernard H.U., Burk R.D., Chen Z., et al. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 2010, 401:70-79.
4. Bouvard V., Baan R., Straif K., et al. A review of human carcinogens-Part B: biological agents. Lancet Oncol 2009, 10:321-322.
5. Bosch F.X., de Sanjose S. Chapter 1: human papillomavirus and cervical cancer-burden and assessment of causality. J Natl Cancer Inst Monogr 2003, (31):3-13.
6. Markowitz L.E., Dunne E.F., Saraiya M., et al. Quadrivalent human papillomavirus vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007, Available at:, Accessed May 25, 2011. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm%3fs_cid%3drr5602a1_e.
7. Jemal A., Simard E.P., Dorel C., et al. Annual report to the nation on the status of cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 2013, 105(3):175-201.
8. Myers E.R., McCrory D.C., Nanda K., et al. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol 2000, 151(12):1158-1171.
9. Herrero R., Hildesheim A., Bratti C., et al. Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica. J Natl Cancer Inst 2000, 92(6):464-474.
10. Castellsague X., de Sanjose S., Aguado T., et al. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre) 2007, HPV and cervical cancer in the world [Report], WHO, ICO, Geneva (Switzerland), Barcelona (Spain), Available at:, Accessed February 7, 2013. http://www.who.int/hpvcentre/en/.
11. Ferlay J., Shin H.R., Bray F., et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127(12):2893-2917.
12. Papanicolaou G.N. A new procedure for staining vaginal smears. Science 1942, 95(2469):438-439.
13. Sahasrabuddhe V., Sherman M.E. Human papillomavirus vaccines for cervical cancer prevention: translating possibility into reality. J Natl Cancer Inst 2012, 104(22):1698-1701.
14. Schiffman M., Wentzensen N., Wacholder S., et al. Human papillomavirus testing in the prevention of cervical cancer. J Natl Cancer Inst 2011, 103(5):368-383.
15. Schiffman M., Castle P.E., Jeronimo J., et al. Human papillomavirus and cervical cancer. Lancet 2007, 370(9590):890-907.
16. Stanley M. Immune responses to human papillomavirus. Vaccine 2006, 24(Suppl 1):S16-S22.
17. Muñoz N., Castellsagué X., de González A.B., et al. Chapter 1: HPV in the etiology of human cancer. Vaccine 2006, 24(Suppl 3). S3/1-10.
18. Schiffman M., Castle P.E. The promise of global cervical-cancer prevention. N Engl J Med 2005, 353(20):2101-2104.
19. Schiller J.T., Lowy D.R. Immunogenicity testing in human papillomavirus virus-like-particle vaccine trials. J Infect Dis 2009, 200:166-171.
20. CDC Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007, 56:RR-2.
21. Centers for Disease Control and Prevention (CDC) FDA licensure of bivalent human papillomavirus vaccine (HPV2 Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2010, 59(20):626-629.
22. GlaxoSmithKline. CDC Advisory Committee recommends Cervarix to prevent cervical cancer in girls and young women. Available at: . Accessed November 10, 2009. http://us.gsk.com/html/media-news/pressreleases/2009/2009_us_pressrelease_10075.htm.
23. Hu D., Goldie S. The economic burden of noncervical human papillomavirus disease in the United States. Am J Obstet Gynecol 2008, 198:500-507.
24. Joseph D.A., Miller J.W., Wu X., et al. Understanding the burden of human papillomavirus-associated anal cancers in the US. Cancer 2008, 113(Suppl 10):2892-2900.
25. Chaturvedi A.K., Engels E.A., Pfeiffer R.M., et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011, 29:4294-4301.
26. Saraiya M. Burden of HPV-associated cancers in the United States. Presentation before the Advisory Committee on Immunization Practices (ACIP), February 24, 2011. Atlanta (GA): US Department of Health and Human Services, CDC; 2011. Available at: . Accessed March 2, 2013. http://www.cdc.gov/vaccines/recs/acip/downloads/mtg-slides-feb11/11-2-hpv-rela-cancer.pdf.
27. Food and Drug Administration Center for Biologics Evaluation and Research. Briefing document for the Vaccines and Related Biological Products Advisory Committee. Subject: Male indication for Gardasil. Available at: . Accessed September 24, 2009. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM181361.pdf.
28. FDA. FDA approves new indication for Gardasil to prevent genital warts in men and boys. 2009 10/16/2009. Available at: . Accessed October 20, 2009. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm187003.htm.
29. Maggard M.A., Beanes S.R., Ko C.Y. Anal canal cancer: a population-based reappraisal. Dis Colon Rectum 2003, 46(11):1517-1523.
30. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2008. Bethesda (MD): National Cancer Institute [based on November 2010 SEER data submission, posted to the SEER web site, 2011]. Available at: . Accessed December 7, 2012. http://seer.cancer.gov/csr/1975_2008/.
31. Johnson L.G., Madeleine M.M., Newcomer L.M., et al. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer 2004, 101:281-288.
32. Centers for Disease Control and Prevention. Human papilloma virus (HPV) associated cancers. Available at: . Accessed March 1, 2013. http://www.cdc.gov/cancer/hpv/statistics/anal.htm.
33. Food and Drug Administration Highlights of prescribing information. Gardasil (human papillomavirus quadrivalent [types 6, 11, 16 and 18]) 2011, Food and Drug Administration, Silver Spring (MD), Available at:, Accessed December 13, 2012. http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm111263.pdf.
34. Giuliano A.R., Palefsky J.M., Goldstone S., et al. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med 2011, 364(5):401-411.
35. Centers for Disease Control and Prevention (CDC) Recommendations for the quadrivalent human papillomavirus vaccine in males - Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011, 60(50):1705-1708.
36. Kreimer A.R., González P., Katki H.A., et al. Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial. Lancet Oncol 2011, 12(9):862-870.
37. Villa L.L., Costa R.L., Petta C.A., et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet 2005, 6(5):271-278.
38. Garland S.M., Hernandez-Avila M., Wheeler C.M., et al. Quadrivalent vaccine against the human papillomavirus to prevent anogenital diseases. N Engl J Med 2007, 356(19):1928-1943.
39. FUTURE II Study Group Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007, 356(19):1915-1927.
40. Kjaer S.K., Sigurdsson K., Iversen O.E., et al. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (types 6/11/16/18) vaccine against high-grade cervical and external genital lesions. Cancer Prev Res (Phila) 2009, 2(10):868-878.
41. Munoz N., Kjaer S.K., 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 2010, 102(5):325-339.
42. Paavonen J., Jenkins D., HPV PATRICIA Study Group, et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet 2007, 369(9580):2161-2170.
43. Lehtinen M., Paavonen J., Wheeler C.M., et al. 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 2012, 13(1):89-99.
44. Schiller J.T., Castellsagué X., Garland S.M. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine 2012, 30S:F123-F138.
45. Wheeler C.M., Castellsagué X., HPV PATRICIA Study Group, et al. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 2012, 13(1):100-110.
46. Malagón T., Drolet M., Boily M.C., et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012, 12(10):781-789.
47. Stanley M., Gissman L., Nardelli-Haeflinger D. Immunobiology of human papillomavirus infection and vaccination-implications for second generation vaccines. Vaccine 2008, 26(Suppl 10):K62-K67.
48. Harper D.M., Franco E.L., Wheeler C., et al. Efficacy of a bivalent L1 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(9447):1757-1765.
49. Villa L.L., Ault K.A., Giuliano A.R., et al. Immunologic responses following administration of a vaccine targeting human papillomavirus types 6, 11, 16, and 18. Vaccine 2006, 24(27-28):5571-5583.
50. Schiller J.T., Castellsague X., Villa L., et al. An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trials. Vaccine 2008, 26(Suppl 10):K53-K61.
51. Denny L, Hendricks B, Gordon C, et al. Safety and immunogenicity of the HPV-16/18 ASO4-adjuvanted vaccine in HIV positive women in South Africa. Abstract no. 599. Presented at AORTIC 7th International Conference. 2011.
52. Available at: . Accessed January 26, 2013. http://www.clinicaltrials.gov/ct2/results%3fterm%3dHPV+and+HIV%26pg%3d1.
53. Reisinger K.S., Block S.L., Lazcano-Ponce E., et al. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatr Infect Dis J 2007, 26(3):201-209.
54. Block S.L., Nolan T., Sattler C., et al. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics 2006, 118(5):2135-2145.
55. Pedersen C., Petaja T., Strauss G., et al. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant. J Adolesc Health 2007, 40(6):564-571.
56. Boehner C.W., Howe S.R., Bernstein D.I., et al. Viral sexually transmitted disease vaccine acceptability among college students. Sex Transm Dis 2003, 30(10):774-778.
57. Einstein M.H., Baron M., Levin M.J., et al. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years. Hum Vaccin 2009, 5(10):705-719.
58. Einstein M.H., Baron M., Levin M.J., et al. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years - Follow up from months 12-24 in a phase III randomized study of healthy women aged 18-45 years. Hum Vaccin 2011, 7(12):1343-1358.
59. Romanowski B., Schwarz T.F., Ferguson L.M., et al. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. Hum Vaccin 2011, 7(12):1374-1386.
60. Kreimer A.R., Rodriguez A.C., Hildesheim A., et al. Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. J Natl Cancer Inst 2011, 103(19):1444-1451.
61. De Vuyst H., Lillo F., Broutet N., et al. HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy. Eur J Cancer Prev 2008, 17:545-554.
62. Harris T.G., Burk R.B., Palefsky J.M., et al. Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results. JAMA 2005, 293:1471-1476.
63. Denny L.A., Franceschi S., de Sanjosé S., et al. Human papillomavirus, human immunodeficiency virus and immunosuppression. Vaccine 2012, 30(Suppl 5):F168-F174.
64. Dempsey A., Cohn L., Dalton V., et al. Worsening disparities in HPV vaccine utilization among 19-26 year old women. Vaccine 2009, 29:528-534.
65. CDC National, state, and local area vaccination coverage among adolescents aged 13-17 years--United States, 2009. MMWR Recomm Rep 2010, 59:1018-1023. Available at:, Accessed February 23, 2013. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6033a1.htm#Tab1.
66. Dempsey A.F., Zimet G.D., Davis R.L., et al. Factors that are associated with parental acceptance of human papillomavirus vaccines: a randomized intervention study of written information about HPV. Pediatrics 2006, 117(5):1486-1493.
67. Wong L.P. Young multiethnic women's attitudes toward the HPV vaccine and HPV vaccination. Int J Gynaecol Obstet 2008, 103(2):131-135.
68. Davis K., Dickman E.D., Ferris D., et al. Human papillomavirus vaccine acceptability among parents of 10- to 15-year-old adolescents. J Low Genit Tract Dis 2004, 8(3):188-194.
69. Zimet G.D., Perkins S.M., Sturm L.A., et al. Predictors of STI vaccine acceptability among parents and their adolescent children. J Adolesc Health 2005, 37(3):179-186.
70. Kahn J.A., Ding L., Huang B., et al. Mothers' intention for their daughters and themselves to receive the human papillomavirus vaccine: a national study of nurses. Pediatrics 2009, 123(6):1439-1445.
71. Stobbe M. Panel recommends a 2nd cervical cancer vaccine as alternative for girls and young women 2009, New York Times, New York.
72. Etter D.J., Zimet G.D., Vaughn R.I. Human papillomavirus vaccine in adolescent women: a 2012 update. Curr Opin Obstet Gynecol 2012, 24:305-310.
73. Dunne E.F., Unger E.R., Sternberg M., et al. Prevalence of HPV infection among females in the United States. JAMA 2007, 297(8):813-819.
74. Ault K.A. Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol 2006, 2006:40470.
75. Huang C.M. Human papillomavirus and vaccination. Mayo Clin Proc 2008, 83(6):701-707.
76. Jain N., Euler G.L., Shefer A., et al. Human papillomavirus (HPV) awareness and vaccination initiation among women in the United States, national immunization survey-adult 2007. Prev Med 2009, 48(5):426-431.
77. Williams W.W., Lu P.J., Singleton J.A., et al. Adult vaccination coverage - United States, 2010. MMWR Recomm Rep 2012, 61(4):66-70.
78. Dempsey A., Cohn L., Dalton V.A., et al. Patient and clinic factors associated with adolescent human papillomavirus vaccine utilization within a university based health system. Vaccine 2010, 28(4):989-995.
79. Barr E., Sings H.L. Prophylactic HPV vaccines: new interventions for cancer control. Vaccine 2008, 26:6244-6257.
80. Graham J., Mishra A. Global challenges of implementing human papillomavirus vaccines. Int J Equity Health 2011, 10:27.
81. GAVI welcomes lower prices for life-saving vaccines 2011, GAVI Alliance, Geneva (Switzerland), Available at:, Accessed August 8, 2011. http://www.gavialliance.org/library/news/press-releases/2011/gavi-welcomes-lower-prices-for-life-saving-vaccines/.
82. Poljak M. Prophylactic human papillomavirus vaccination and primary prevention of cervical cancer: issues and challenges. Clin Microbiol Infect 2012, 18(Suppl 5):64-69.
83. LaMontagne D.S., Barge S., Thi Le N., et al. Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middle-income countries. Bull World Health Organ 2011, 89:821-830.
84. Donovan B., Franklin N., Guy R., et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis 2011, 11:39-44.
85. Read T.R., Hocking J.S., Chen M.Y., et al. The near disappearance of genital warts in young women 4 years after commencing a national human papillomavirus (HPV) vaccination programme. Sex Transm Infect 2011, 87:544-547.
86. Brotherton J.M., Fridman M., May C., et al. Early impact of the HPV vaccination program on cervical abnormalities in Victoria, Australia: an ecological study. Lancet 2011, 377:2085-2092.
87. Peres J. For cancers caused by HPV, two vaccines were just the beginning. J Natl Cancer Inst 2011, 103(5):360-362.
88. Seitz H., Schmitt M., Böhmer G., et al. Natural variants in the major neutralizing epitope of human papillomavirus minor capsid protein L2. Int J Cancer 2013, 132(3):E139-E148.
89. Nakao S., Mori S., Kondo K., et al. Monoclonal antibodies recognizing cross-neutralization epitopes in human papillomavirus 16 minor capsid protein L2. Virology 2012, 434(1):110-117.
90. Nieto K., Weghofer M., Sehr P., et al. Development of AAVLP(HPV16/31L2) particles as broadly protective HPV vaccine candidate. PLoS One 2012, 7(6):e39741.
91. Yoon S.W., Lee T.Y., Kim S.J., et al. Oral administration of HPV-16 L2 displayed on Lactobacillus casei induces systematic and mucosal cross-neutralizing effects in Balb/c mice. Vaccine 2012, 30(22):3286-3294.
92. Franceschi S., Cuzick J., Herrero R., et al. EUROGIN 2008 roadmap on cervical cancer prevention. Int J Cancer 2009, 125(10):2246-2255.
93. Van de Velde N., Boily M.C., Drolet M., et al. Population-level impact of the bivalent, quadrivalent, and nonavalent human papillomavirus vaccines: a model-based analysis. J Natl Cancer Inst 2012, 104(22):1712-1723.
94. Hung C.F., Ma B., Monie A., et al. Therapeutic human papillomavirus vaccines: current clinical trials and future directions. Expert Opin Biol Ther 2008, 8(4):421-439.
95. Joura E.A., Garland S.M., Paavonen J., FUTURE I and II Study Group, et al. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. BMJ 2012, 344:e1401.
96. FUTURE I/II Study Group, Dillner J., Kjaer S.K., et al. Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. BMJ 2010, 341:c3493.
97. Ault K.A., Future II Study Group 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 2007, 369(9576):1861-1868.
98. Brown D.R., Kjaer S.K., Sigurdsson K., et al. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years. J Infect Dis 2009, 199(7):926-935.
99. Paavonen J., Naud P., HPV PATRICIA Study Group, 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. Lancet 2009, 374(9686):301-314.