김 미 경·노 재 홍·송 용 상 | 서울의대 산부인과 | Mi-Kyung Kim, MD·Jae Hong No, MD·Yong -Sang Song, MD
Department of Obstetrics and Gynecology, Seoul National University College of Medicine
E – mail : yssong@snu.ac.kr

J Korean Med Assoc 2009; 52(12): 1180 – 1186

http://synapse.koreamed.org/Synapse/Data/PDFData/0119JKMA/jkma-52-1180.pdf

Abstract

Cervical cancer is the second most common cancer affecting women worldwide. Cervical
cancer is caused by persistent infection with high-risk types of human papillomavirus (HPV).
The most common oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Recently, two HPV vaccines, quadrivalent (HPV 6, 11, 16, 18) and bivalent
(HPV 16, 18) vaccines, have been licensed and are now marketed in Korea. HPV vaccines are
prepared from virus-like particles (VLPs) produced by recombinant technology. Clinical trials
have confirmed that both vaccines have high efficiency against persistent infection of HPV 16 or 18 and moderate to severe precancerous lesions. In women who have no evidence of past or current infection with the HPV genotypes in the vaccine, both vaccines show > 90% protection against persistent HPV infection for up to 5 years after vaccination. In addition, vaccine efficacy against precancerous lesions associated with HPV 16/18 was reported to be 100%. Although most clinical trials to date have investigated the effectiveness of HPV vaccines in young females, elderly females and males may also be candidates for HPV vaccines. Since HPV vaccines are prophylactic, the largest impact of vaccination is expected to result from high coverage of young adolescents before exposure to HPV. Cervical cancer screening will still be required, even after HPV vaccines are introduced, although the screening program may need to be adapted to achieve cost-effective reductions in the burden of cervical cancer prevention strategies.

Keywords: Cervical cancer; Human papillomavirus; Vaccination; Prevention
핵 심 용 어: 자궁경부암; 인유두종바이러스; 백신; 예방

결 론
HPV 백신의 도입으로 향후 자궁경부암의 발생 및 사망
률의 감소로 인한 사회적인 부담이 줄어들 것으로 예상하고
있다. HPV 백신의 효과를 극대화시키기 위해선 백신에 대
한 적극적인 권장과 교육이 필요할 것이다. 향후 백신 효과
의 지속기간, 추가접종의 필요성, 면역원성과 백신효능의
관계, 안전성, 비용효과 분석, 한정된 사회적 재원에서의 백
신 투여 전략 등에 대한 추가 연구가 필요하다. 무엇보다 중
요한 것은 백신으로 모든 자궁경부암이 예방되는 것이 아니
므로 지속적인 자궁경부암 선별검사의 중요성을 주지시키
는 것이다.

참고문헌
11. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,
2002. CA Cancer J Clin 2005; 55: 74-108.
12. Chung HH, Jang MJ, Jung KW, Won YJ, Shin HR, Kim JW
Lee HP. Cervical cancer incidence and survival in Korea: 1993-
2002. Int J Gynecol Cancer 2006; 16: 1833-1838.
13. Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC,
Patel SS, Markowitz LE. Prevalence of HPV infection among
females in the United States. Jama 2007; 297: 813-819.
14. Koshiol J, Lindsay L, Pimenta JM, Poole C, Jenkins D, Smith
JS. Persistent human papillomavirus infection and cervical
neoplasia: a systematic review and meta-analysis. Am J
Epidemiol 2008; 168: 123-137.
15. Clifford GM, Smith JS, Plummer M, Munoz N, Franceschi S.
Human papillomavirus types in invasive cervical cancer
worldwide: a meta-analysis. Br J Cancer 2003; 88: 63-73.
16. Parkin DM, Bray F. Chapter 2: The burden of HPV-related
cancers. Vaccine 2006; 24(Suppl 3): S3/11- 25.
17. Derkay CS, Wiatrak B. Recurrent respiratory papillomatosis: a
review. Laryngoscope 2008; 118: 1236 -1247.
18. Stanley M. Immune responses to human papillomavirus.
Vaccine 2006; 24(Suppl 1): S16-22.
19. Carter JJ, Koutsky LA, Hughes JP, Lee SK, Kuypers J, Kiviat
N, Galloway DA. Comparison of human papillomavirus types
16, 18, and 6 capsid antibody responses following incident
infection. J Infect Dis 2000; 181: 1911-1919.
10. Hagensee ME, Yaegashi N, Galloway DA. Self-assembly of
human papillomavirus type 1 capsids by expression of the L1
protein alone or by coexpression of the L1 and L2 capsid
proteins. J Virol 1993; 67: 315-322.
11. Mao C, Koutsky LA, Ault KA, Wheeler CM, Brown DR, Wiley
DJ, Alvarez FB, Bautista OM, Jansen KU, Barr E. Efficacy of
human papillomavirus-16 vaccine to prevent cervical
intraepithelial neoplasia: a randomized controlled trial. Obstet
Gynecol 2006; 107: 18-27.
12. Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano
AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M,
Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman
RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms
GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU,
Esser MT, Sings HL, Saah AJ, Barr E. 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 Oncol 2005; 6: 271- 278.
13. Garlard SM, Hernandez-Avila M, Wheeler CM, Perez G,
Harper DM, Leodolter S, Tang GW, Ferris DG, Steben M,
Bryan J, Taddeo FJ, Railkar R, Esser MT, Sings HL, Nelson M,
Boslego J, Sattler C, Barr E, Koutsky LA. Quadrivalent vaccine
against human papillomavirus to prevent anogenital diseases.
N Engl J Med 2007; 356: 1928-1943.
14. Quadrivalent vaccine against human papillomavirus to prevent
high-grade cervical lesions. N Engl J Med 2007; 356: 1915-
1927.
15. Ault KA. Effect of prophylactic human papillomavirus L1 viruslike-
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:
1861-1868.
16. Munoz N, Manalastas R, Jr., Pitisuttithum P, Tresukosol D,
Monsonego J, Ault K, Clavel C, Luna J, Myers E, Hood S,
Bautista O, Bryan J, Taddeo FJ, Esser MT, Vuocolo S, Haupt
RM, Barr E, Saah A. 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 2009; 373: 1949-1957.
17. Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen
OE, Olsson SE, Hoye J, Steinwall M, Riis-Johannessen G,
Andersson-Ellstrom A, Elfgren K, Krogh G, Lehtinen M, Malm
C, Tammns GM, Giacoletti K, Lupinacci L, Railkar R, Taddeo
FJ, Bryan J, Esser MT, Sings HL, Saah AJ, Barr E. High
sustained efficacy of a prophylactic quadrivalent human papillomavirus
types 6/11/16/18 L1 virus-like particle vaccine
through 5 years of follow-up. Br J Cancer 2006; 95: 1459-
1466.
18. Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C,
Iversen OE, Hoye J, Stienwall M, Riis-Johannessen G,
Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M,
Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT,
Vuocolo SC, Saah AJ, Barr E. Induction of immune memory
following administration of a prophylactic quadrivalent human
papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle
(VLP) vaccine. Vaccine 2007; 25: 4931- 4939.
19. Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN,
Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR,
Hedrick J, Jaisamram U, Limson G, Garland S, Szarewski A,
Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX,
Jenkins D, Hardt K, Jahaf T, Descamps D, Struyf F, Lehtinen
M, Dubin G, Greenacre M. 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: 301- 314.
20. Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski
B, Roteli-Martins CM, Jenkins D, Schuind A, Costa
Clemens SA, Dubin G. Sustained efficacy up to 4.5 years of a
bivalent L1 virus-like particle vaccine against human
papillomavirus types 16 and 18: follow-up from a randomised
control trial. Lancet 2006; 367: 1247-1255.
21. Smith JF, Brownlow M, Brown M, Kowalski R, Esser MT,
Ruiz W, Barr E, Brown DR, Bryan JT. Antibodies from women
immunized with Gardasil cross-neutralize HPV 45 pseudovirions.
Hum Vaccin 2007; 3: 109 -115.
22. Brown DR, Kjaer Sk, Sigurdsson K, Iversen OE, Hernandez-
Avila M, Wheeler CM, Perez G, Koutsky LA, Tay EH, Garcia P,
Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW,
Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Joura
EA, Kurman RJ, Majewski S, Munoz N, Myers ER, Villa LL,
Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lupinacci LC,
Giacoletti KE, Sings HL, James M, Hesley TM, Barr E. 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:
926-935.
23. Pataja T, Keranen H, Karppa T, Kawa A, Lantela S, Siitari-
Mattila M, Levanen H, Tocklin T, Godeaux O, Lehtinen M,
Dubin G. Immunogenicity and safety of human papillomavirus
(HPV)-16/18 AS04-adjuvanted vaccine in healthy boys aged
10-18 years. J Adolesc Health 2009; 44: 33-40.
24. Ronco G, Giorgi Rossi P. New paradigms in cervical cancer
prevention: opportunities and risks. BMC Womens Health
2008; 8: 23.
25. Franco EL, Cuzick J. Cervical cancer screening following
prophylactic human papillomavirus vaccination. Vaccine 2008;
26 Suppl 1: A16 -23.