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Merck's Statement
May 9, 2007 6:24 p.m.
New England Journal of Medicine Publishes New Data on GARDASIL®, Merck's Cervical Cancer Vaccine
WHITEHOUSE STATION, N.J., May 9, 2007 - Today, the New England Journal of Medicine is publishing results from two Phase III studies of Merck's cervical cancer vaccine, GARDASIL [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]. In the first study, GARDASIL provided 100 percent protection against cervical, vaginal and vulvar diseases caused by the four HPV types GARDASIL is designed to protect against, HPV types 6, 11, 16, and 18. In the second study, GARDASIL provided 98 percent protection against advanced cervical pre-cancers caused by the two primary cancer-causing HPV types, HPV 16 and 18. These significant results, observed in 15- to 26-year-old women who were not infected with the relevant HPV types when they began the study, were sustained through an average of three years of participation in the trials, including an additional year of follow up since data were presented to the U.S. Food and Drug Administration (FDA) for approval of GARDASIL.
"In these two studies, GARDASIL demonstrated significant protection against serious HPV-related diseases, including high-grade cervical pre-cancers, in women not previously exposed to the relevant HPV types targeted by the vaccine," said Kevin Ault, M.D., associate professor, Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta. "Widespread immunization of 11- to 26-year-old girls and women with GARDASIL, along with continued screening, will help decrease the burden of cervical cancer and other HPV-related diseases."
It is estimated that in 2007, cervical cancer will strike more than 11,000 women in the U.S. and nearly 500,000 women around the world. GARDASIL helps protect against the four HPV types - 6, 11, 16 and 18 - that cause the most disease, including 70 percent of cervical cancer cases and 90 percent of cases of genital warts. All four types cause a large number of "abnormal" Pap test results and low-grade cervical lesions.
"My fellow investigators around the world are proud of these data and their contribution to our understanding of the impact of GARDASIL on risk for development of cervical, vulvar, and vaginal diseases caused by HPV 6, 11, 16, and 18," said Eliav Barr, M.D., executive director of Biologics Clinical Research and head of the HPV Vaccine Program, Merck Research Laboratories. "In women not infected with the four HPV types targeted by GARDASIL, GARDASIL reduced cervical disease caused by the relevant HPV types. And, across the larger study population, GARDASIL also reduced the overall burden of cervical, vulvar, and vaginal HPV diseases caused by HPV types targeted by the vaccine and by other HPV types."
GARDASIL was approved by the FDA on June 8, 2006, and is recommended for use by girls and women ages 11 to 26 by the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. GARDASIL is indicated for the prevention of HPV types 16- and 18- related cervical cancer, non-invasive cervical cancer [cervical intraepithelial neoplasia (CIN) grade 3 and adenocarcinoma in situ (AIS)], cervical pre-cancers [cervical intraepithelial neoplasia (CIN) grade 2], vulvar pre-cancers [vulvar intraepithelial neoplasia (VIN) 2/3)] and vaginal pre-cancers [vaginal intraepithelial neoplasia (VaIN) 2/3], and for the prevention of genital warts and low-grade cervical lesions (CIN 1) caused by HPV types 6, 11, 16 and 18. GARDASIL is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine.
Studies assessed CIN 2/3, the most meaningful efficacy measure
The studies, FUTURE I and FUTURE II, are phase III, prospective, double-blind, placebo-controlled randomized studies conducted in 29 countries. The women who participated in the trials were 15 to 26 years old at enrollment; they received three doses of either GARDASIL or placebo at day one, month two and month six. The primary analyses of these trials evaluated the efficacy of GARDASIL compared to placebo in women who were free of infection with the relevant HPV types (6, 11, 16 and/or 18) when they started the study, remained free of infection with the relevant HPV types through month seven, received all three doses of GARDASIL within one year and had no protocol violations.
FUTURE I was designed to evaluate the impact of GARDASIL on the incidence of cervical lesions and pre-cancers (CIN 1-3), vulvar and vaginal external lesions and pre-cancers (VIN 1-3 and VaIN 1-3) and external genital warts caused by the four HPV types targeted by the vaccine (HPV 6, 11, 16 and 18). FUTURE II was designed to evaluate the impact of GARDASIL on pre-cancers and non-invasive cancers (CIN 2/3, AIS) caused by HPV 16 and 18. Prevention of advanced, or high grade cervical pre-cancerous lesions -- CIN 2/3 or AIS -- has been identified by the FDA and World Health Organization as the most meaningful indicator of cancer efficacy for a cervical cancer vaccine.
Results showed that GARDASIL provided significant protection in women not previously exposed to HPV types targeted by the vaccine
In FUTURE I, after an average follow-up of three years, GARDASIL provided 100 percent protection from HPV 6-, 11-, 16- and 18-related VIN 1-3, VaIN 1-3 and genital warts; no cases were observed in the vaccine group (n=2,261) compared to 60 cases in the placebo group (n=2,279). GARDASIL was also 100 percent effective for the prevention of HPV 6-, 11-, 16-, or 18-related CIN 1-3; there were no cases observed in the vaccine group (n=2,241) compared to 65 cases in the placebo group (n=2,258).
In FUTURE II, after an average follow-up of three years, GARDASIL was 98 percent effective in preventing high-grade cervical pre-cancers associated with HPV types 16 and 18; one case of CIN 3 was observed in the vaccine group (n=5,305) compared to 42 cases in the placebo group (n=5,260).
Studies assessed efficacy of GARDASIL in the general population of women
The studies also assessed the efficacy of GARDASIL in the general population of women, including those infected with HPV (and who may have had HPV-related disease) at the start of the trials. In FUTURE I, GARDASIL reduced the rate of cervical lesions caused by vaccine or other HPV types by 20 percent; 344 cases were observed in the vaccine group (n= 2,723); 421 cases were observed in the placebo group (n=2,732). GARDASIL reduced the rate of vaginal or vulvar lesions and genital warts caused by vaccine or other HPV types by 34 percent; 104 cases were observed in the vaccine group (n= 2,723); 157 cases were observed in the placebo group (n=2,732). In FUTURE II, vaccination with GARDASIL reduced the rate of CIN 2/3 and AIS caused by vaccine or other HPV types by 17 percent; 219 cases were observed in the vaccine group (n= 6,087); 266 cases were observed in the placebo group (n=6,080). In both studies, the majority of lesions occurred among women who were already HPV-infected at the start of vaccination. Vaccination with GARDASIL did not change the course of these pre-existing infections. Infections present at the start of vaccination caused most of the lesions in the early period of follow-up; however, over three years, the impact of the vaccine became more apparent, as lesions caused by new infections with vaccine HPV types were observed in the placebo group but not in the vaccine group.
In both studies, the adverse events observed were similar to what has been previously reported.
Additional important information about GARDASIL
The health-care provider should inform the patient, parent or guardian that vaccination does not substitute for routine cervical cancer screening. Women who receive GARDASIL should continue to undergo cervical cancer screening per standard of care.
Vaccination with GARDASIL may not result in protection in all vaccine recipients. GARDASIL is not intended to be used for treatment of active genital warts; cervical cancer; CIN, VIN, or VaIN. GARDASIL has not been shown to protect against disease due to other HPV types.
In clinical studies for GARDASIL, vaccine-related adverse experiences that were observed at a frequency of at least 1.0 percent among recipients of GARDASIL and also greater than those observed among recipients of placebo, respectively, were pain (83.9 percent vs. 75.4 percent), swelling (25.4 percent vs. 15.8 percent), erythema (24.6 percent vs. 18.4 percent), fever (10.3 percent vs. 8.6 percent), nausea (4.2 percent vs. 4.1 percent), pruritis (3.1 percent vs. 2.8 percent) and dizziness (2.8 percent vs. 2.6 percent).
Dosage and administration for GARDASIL
GARDASIL is a ready-to-use, three-dose, intramuscular vaccine. GARDASIL should be administered in three separate intramuscular injections in the upper arm or upper anterior thigh over a six-month period. The following dosage schedule is recommended: first dose at elected date, second dose two months after the first dose and the third dose six months after the first dose.
GARDASIL is widely available throughout the United States
There is broad private and public health insurance coverage for GARDASIL. Health plans covering approximately 98 percent of privately insured lives in the U.S. (currently more than 140 insurance plans) have implemented coverage for GARDASIL; however, individual benefit coverage and rates provided by health plans may vary.
GARDASIL was also added to the Vaccines for Children (VFC) Program on November 1, 2006, providing coverage for many who do not have private health insurance. All of the 55 immunization projects in the U.S. have adopted GARDASIL and most are filling provider orders.
Merck has also initiated a new patient assistance program for vaccines. Through this program, currently available in private physicians' offices and private clinics, Merck is making available, free of charge, GARDASIL and other Merck vaccines indicated for use in individuals ages 19 and older who are uninsured and who are unable to afford vaccines.
GARDASIL is approved in 70 countries
GARDASIL (sold in some countries as SILGARD® has been approved in 70 countries, including the United States, the 27 countries of the European Union, Mexico, Australia, Taiwan, Canada, New Zealand and Brazil, and additional applications are currently under review with regulatory agencies in many more countries around the world.
Merck will donate free vaccine to the non-profit organization PATH to support demonstration studies designed to accelerate the availability of cervical cancer vaccines in the most impoverished nations. PATH is funded by a grant from the Bill & Melinda Gates Foundation. Merck is also working with India's Council of Medical Research to study GARDASIL in India. Merck will make its new vaccines, including GARDASIL, available to developing world countries at dramatically lower prices.
HPV is a common infection
In the United States, approximately 20 million people are infected with HPV, and approximately 80 percent of females will have acquired HPV by age 50. For most people, HPV goes away on its own; however in some, certain high-risk types of HPV, if unrecognized and untreated, can lead to cervical cancer. Cervical cancer is the second most common cause of cancer death in women worldwide, resulting in nearly a half-million diagnoses and 240,000 deaths each year. It is estimated that in 2007, there will be approximately 11,150 new cases of cervical cancer and 3,700 deaths in the United States. Approximately 6,000 cases of vulvar or vaginal cancer are diagnosed annually in the U.S.
Certain low-risk types of HPV cause genital warts and can lead to abnormal Pap results. Approximately one million cases of genital warts occur each year in the United States and an estimated 32 million cases occur worldwide. Additionally, there are an estimated 4.7 million abnormal Pap results that require follow-up each year in the United States. At least 3 million of these results are caused by some type of HPV.
Other Information about GARDASIL
In 1995, Merck entered into a license agreement and research collaboration with CSL Limited of Australia relating to technology used in GARDASIL. GARDASIL also is the subject of other third-party licensing agreements.
Merck recently announced that it submitted a supplemental Biologics License Application (sBLA) to the FDA that includes efficacy data showing GARDASIL offers some protection against additional cervical cancer causing HPV types responsible for greater than 10 percent of cervical cancers, data on protection against additional gynecological cancers -- vaginal and vulvar -- and data on immune memory.
Source: Merck
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Merck's Statement
May 9, 2007 6:24 p.m.
New England Journal of Medicine Publishes New Data on GARDASIL®, Merck's Cervical Cancer Vaccine
Merck声明
2007年5月9日下午 6:24
《新英格兰医学杂志》发表默克公司子宫颈癌疫苗GARDASIL®的最新数据
WHITEHOUSE STATION, N.J., May 9, 2007 - Today, the New England Journal of Medicine is publishing results from two Phase III studies of Merck's cervical cancer vaccine, GARDASIL [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]. In the first study, GARDASIL provided 100 percent protection against cervical, vaginal and vulvar diseases caused by the four HPV types GARDASIL is designed to protect against, HPV types 6, 11, 16, and 18. In the second study, GARDASIL provided 98 percent protection against advanced cervical pre-cancers caused by the two primary cancer-causing HPV types, HPV 16 and 18. These significant results, observed in 15- to 26-year-old women who were not infected with the relevant HPV types when they began the study, were sustained through an average of three years of participation in the trials, including an additional year of follow up since data were presented to the U.S. Food and Drug Administration (FDA) for approval of GARDASIL.
2007年5月9日WHITEHOUSE STATION, N.J.报道 今天《新英格兰医学杂志》发表了默克公司子宫颈癌疫苗GARDASI（人乳头瘤病毒 6、11、16、18型四联重组疫苗）的两个临床3期结果。第一个结果，GARDASIL对GARDASIL所针对的四种人乳头瘤病毒引起的宫颈、阴道和外阴疾病有100%的保护作用。在第二个研究中，GARDASIL对于两种主要的致癌型病毒HPV 16 和HPV18引起的子宫颈癌前病变进展有98%的防护作用。这些研究结果是在15到26岁女性中获得的，她们在研究开始时并未感染相关的人乳头瘤病毒，研究持续了3年，其中包括由于向美国食品和药品管理局提交数据申请获批而增加的1年随访期。
"In these two studies, GARDASIL demonstrated significant protection against serious HPV-related diseases, including high-grade cervical pre-cancers, in women not previously exposed to the relevant HPV types targeted by the vaccine," said Kevin Ault, M.D., associate professor, Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta. "Widespread immunization of 11- to 26-year-old girls and women with GARDASIL, along with continued screening, will help decrease the burden of cervical cancer and other HPV-related diseases."
“在这两项研究中，GARDASIL在先前未接触过疫苗针对的几种HPV亚型的妇女中显示出明显的预防严重HPV相关疾病的能力，包括高度恶性子宫颈癌前病变。”亚特兰大艾莫雷大学医学院妇产科妇科肿瘤学副教授、医学博士Kevin Ault说：“在11到26岁的女性中广泛的免疫接种GARDASIL，同时不断筛查，能减少子宫颈癌和其他HPV相关疾病的发病。”
It is estimated that in 2007, cervical cancer will strike more than 11,000 women in the U.S. and nearly 500,000 women around the world. GARDASIL helps protect against the four HPV types - 6, 11, 16 and 18 - that cause the most disease, including 70 percent of cervical cancer cases and 90 percent of cases of genital warts. All four types cause a large number of "abnormal"
Pap test results and low-grade cervical lesions.
据估计，2007年美国的子宫颈癌患者将会超过11000人，全球将有将近500000患者。GARDASIL有助于预防四种HPV亚型引起的疾病，这四种HPV（HPV6, 11, 16 和18型）引发的疾病占HPV引发疾病的大多数，包括70%的子宫颈癌和90%的生殖器疣。这四种病毒都可导致巴氏试验异常和低度恶性的宫颈损伤。
"My fellow investigators around the world are proud of these data and their contribution to our understanding of the impact of GARDASIL on risk for development of cervical, vulvar, and vaginal diseases caused by HPV 6, 11, 16, and 18," said Eliav Barr, M.D., executive director of Biologics Clinical Research and head of the HPV Vaccine Program, Merck Research Laboratories. "In women not infected with the four HPV types targeted by GARDASIL, GARDASIL reduced cervical disease caused by the relevant HPV types. And, across the larger study population, GARDASIL also reduced the overall burden of cervical, vulvar, and vaginal HPV diseases caused by HPV types targeted by the vaccine and by other HPV types."
默克实验室生物制品临床研究执行主任和HPV疫苗项目主管Eliav Barr博士说：“我的各国同事对这个结果感到非常自豪，他们为探知GARDASIL对HPV 6, 11, 16,和18型引起的宫颈、外阴和阴道疾病发病危险的影响做出了巨大的贡献。在那些未感染GARDASIL所针对的这四种HPV的妇女中，GARDASIL减少了由这四种病毒引发的宫颈疾病。同时，在更大样本的群体中，GARDASIL不仅降低了疫苗所针对的HPV病毒导致的宫颈、外阴和阴道疾病，而且还减少了其他类型HPV引发的宫颈、外阴和阴道疾病。”
GARDASIL was approved by the FDA on June 8, 2006, and is recommended for use by girls and women ages 11 to 26 by the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. GARDASIL is indicated for the prevention of HPV types 16- and 18- related cervical cancer, non-invasive cervical cancer [cervical intraepithelial neoplasia (CIN) grade 3 and adenocarcinoma in situ (AIS)], cervical pre-cancers [cervical intraepithelial neoplasia (CIN) grade 2], vulvar pre-cancers [vulvar intraepithelial neoplasia (VIN) 2/3)] and vaginal pre-cancers [vaginal intraepithelial neoplasia (VaIN) 2/3], and for the prevention of genital warts and low-grade cervical lesions (CIN 1) caused by HPV types 6, 11, 16 and 18. GARDASIL is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine.
GARDASIL于2006年6月8日被美国食品和药品管理局批准，同时美国疾病控制中心和免疫接种顾问委员会推荐11到26岁的女性使用这种疫苗。研究表明GARDASIL可以预防HPV16和18型相关的子宫颈癌、非侵入性宫颈癌（宫颈上皮瘤样病变样病变(CIN)3级和原位腺癌(AIS)）、宫颈癌前病变（宫颈上皮瘤样病变(CIN)2级）、外阴癌前病变（外阴上皮瘤样病变样病变(VIN) 2/3级）和阴道癌前病变（阴道上皮瘤样病变(VaIN) 2/3级），同时对于HPV6、11、16和18型引起的生殖器疣和低度恶性的宫颈损伤(CIN 1级)具有保护作用。GARDASIL禁用于对疫苗活性成分或佐剂过敏者。
Studies assessed CIN 2/3, the most meaningful efficacy measure
对CIN 2/3（最有意义的指标）效用的研究
The studies, FUTURE I and FUTURE II, are phase III, prospective, double-blind, placebo-controlled randomized studies conducted in 29 countries. The women who participated in the trials were 15 to 26 years old at enrollment; they received three doses of either GARDASIL or placebo at day one, month two and month six. The primary analyses of these trials evaluated the efficacy of GARDASIL compared to placebo in women who were free of infection with the relevant HPV types (6, 11, 16 and/or 18) when they started the study, remained free of infection with the relevant HPV types through month seven, received all three doses of GARDASIL within one year and had no protocol violations.
研究中的FUTURE I 和 FUTURE II是在29个国家进行的前瞻性的、双盲的、安慰剂对照的随机试验。参与者是年龄在15到26岁之间的女性，她们分别在第一天、两个月、六个月接受了共3次的GARDASIL或安慰剂注射。研究主要分析GARDASIL与安慰剂相比的有效性，所有的受试者在研究初期均未感染过这四种HPV(6, 11, 16 和/或18型)，而且在7个月中保持未被感染，并在一年内完成GARDASIL的三次剂量，没有违反实验设计。
FUTURE I was designed to evaluate the impact of GARDASIL on the incidence of cervical lesions and pre-cancers (CIN 1-3), vulvar and vaginal external lesions and pre-cancers (VIN 1-3 and VaIN 1-3) and external genital warts caused by the four HPV types targeted by the vaccine (HPV 6, 11, 16 and 18). FUTURE II was designed to evaluate the impact of GARDASIL on pre-cancers and non-invasive cancers (CIN 2/3, AIS) caused by HPV 16 and 18. Prevention of advanced, or high grade cervical pre-cancerous lesions -- CIN 2/3 or AIS -- has been identified by the FDA and World Health Organization as the most meaningful indicator of cancer efficacy for a cervical cancer vaccine.
FUTURE I评估GARDASIL对疫苗针对的四种HPV所致的宫颈损伤和癌前病变(宫颈上皮瘤样病变 1-3级)、外阴和阴道损伤和癌前病变（外阴上皮瘤样病变1-3级和阴道上皮瘤样病变1-3级）以及生殖器疣的发病率的影响。FUTURE II 主要是评价GARDASIL对HPV 16 和 18导致的癌前期和非侵入性癌(宫颈上皮瘤样病变 2/3级, 原位腺癌)的影响。美国食品和药品管理局和世界卫生组织将能够阻止高度恶性癌前期病变(宫颈上皮瘤样病变 2/3级, 原位腺癌)进展作为子宫颈癌疫苗有效的最有意义的指征。
Results showed that GARDASIL provided significant protection in women not previously exposed to HPV types targeted by the vaccine
结果表明GARDASIL对未感染过这几种病毒亚型的女性有明显的保护作用。
In FUTURE I, after an average follow-up of three years, GARDASIL provided 100 percent protection from HPV 6-, 11-, 16- and 18-related VIN 1-3, VaIN 1-3 and genital warts; no cases were observed in the vaccine group (n=2,261) compared to 60 cases in the placebo group (n=2,279). GARDASIL was also 100 percent effective for the prevention of HPV 6-, 11-, 16-, or 18-related CIN 1-3; there were no cases observed in the vaccine group (n=2,241) compared to 65 cases in the placebo group (n=2,258).
FUTURE I中，平均三年的随访期后，GARDASIL显示了100%的预防HPV 6-, 11-, 16- 和18相关的外阴上皮瘤样病变（VIN 1-3）、阴道上皮瘤样病变( VaIN 1-3)和生殖器疣等疾病的效果：在2261名的疫苗组中没有1例患者出现，而安慰剂对照组中的2279例中出现了60个病例。GARDASIL对于预防HPV 6-, 11-, 16-, 和18相关的宫颈上皮瘤样病变（CIN 1-3）也是100%的有效：2241人接受疫苗后无一人发病，而2258名对照组中则有65名患者。
In FUTURE II, after an average follow-up of three years, GARDASIL was 98 percent effective in preventing high-grade cervical pre-cancers associated with HPV types 16 and 18; one case of CIN 3 was observed in the vaccine group (n=5,305) compared to 42 cases in the placebo group (n=5,260).
FUTURE II中，平均三年随访期后，GARDASIL 预防HPV 16和HPV18型相关的高度恶性癌前期病变的有效率达到98%：5305名疫苗组中仅发现1位宫颈上皮瘤样病变3级患者，对照组（5260人）中有42例。
Studies assessed efficacy of GARDASIL in the general population of women
评价GARDASIL在普通女性群体中有效性的研究
The studies also assessed the efficacy of GARDASIL in the general population of women, including those infected with HPV (and who may have had HPV-related disease) at the start of the trials. In FUTURE I, GARDASIL reduced the rate of cervical lesions caused by vaccine or other HPV types by 20 percent; 344 cases were observed in the vaccine group (n= 2,723); 421 cases were observed in the placebo group (n=2,732). GARDASIL reduced the rate of vaginal or vulvar lesions and genital warts caused by vaccine or other HPV types by 34 percent; 104 cases were observed in the vaccine group (n= 2,723); 157 cases were observed in the placebo group (n=2,732). In FUTURE II, vaccination with GARDASIL reduced the rate of CIN 2/3 and AIS caused by vaccine or other HPV types by 17 percent; 219 cases were observed in the vaccine group (n= 6,087); 266 cases were observed in the placebo group (n=6,080). In both studies, the majority of lesions occurred among women who were already HPV-infected at the start of vaccination. Vaccination with GARDASIL did not change the course of these pre-existing infections. Infections present at the start of vaccination caused most of the lesions in the early period of follow-up; however, over three years, the impact of the vaccine became more apparent, as lesions caused by new infections with vaccine HPV types were observed in the placebo group but not in the vaccine group.
研究也评估了GARDASIL在普通女性群体中的有效性，这个群体包括在实验开始时即已感染了HPV和可能患有HPV相关疾病的人。在FUTURE I，GARDASIL降低了宫颈损伤20%：疫苗组2723例中观察到344个病例，对照组2732人中有421病例；降低外阴和阴道损伤和生殖器疣34%：疫苗组2723例中104例，对照组2732例中有157例。在FUTURE II中，接种GARDASIL减少宫颈上皮瘤样病变2/3级和原位腺癌发生率17%：疫苗组6087例中有219例，对照组6080例中有266例。这两个研究中，大多数损伤发生在那些研究初期即已感染了HPV的女性中。接种GARDASIL并不能改变已感染患者的病程，疫苗接种时即已感染病毒是随访早期大多数损伤的病因，但是，三年后，疫苗的作用开始变得明显，此时由新感染疫苗HPV型所致的损伤只在对照组出现，在疫苗组并未发现。
In both studies, the adverse events observed were similar to what has been previously reported.
这两个研究中，观察到的副作用和先前的报道是相似的。
Additional important information about GARDASIL
关于GARDASIL的其他重要信息
The health-care provider should inform the patient, parent or guardian that vaccination does not substitute for routine cervical cancer screening. Women who receive GARDASIL should continue to undergo cervical cancer screening per standard of care.
保健师应该告知患者、父母或监护人，疫苗并不能取代常规的子宫颈癌筛查。接受GARDASIL的女性应该按照护理标准继续接受子宫颈癌筛查。
Vaccination with GARDASIL may not result in protection in all vaccine recipients. GARDASIL is not intended to be used for treatment of active genital warts; cervical cancer; CIN, VIN, or VaIN. GARDASIL has not been shown to protect against disease due to other HPV types.
GARDASIL接种可能并不是对所有的接种者都有效，它也不能用于治疗生殖器疣、子宫颈癌、子宫颈上皮瘤样病变、外阴上皮瘤样病变和阴道上皮瘤样病变。同时对于其他类型HPV感染引起的疾病GARDASIL没有预防作用。
In clinical studies for GARDASIL, vaccine-related adverse experiences that were observed at a frequency of at least 1.0 percent among recipients of GARDASIL and also greater than those observed among recipients of placebo, respectively, were pain (83.9 percent vs. 75.4 percent), swelling (25.4 percent vs. 15.8 percent), erythema (24.6 percent vs. 18.4 percent), fever (10.3 percent vs. 8.6 percent), nausea (4.2 percent vs. 4.1 percent), pruritis (3.1 percent vs. 2.8 percent) and dizziness (2.8 percent vs. 2.6 percent).
在GARDASIL的临床研究中，疫苗副作用发生率至少为1%，比安慰剂对照组的稍高，副作用主要是疼痛 (疫苗组83.9 %，对照组 75.4 %), 肿胀(疫苗组25.4 %，对照组15.8 %), 红斑(疫苗组24.6%， 对照组18.4 %), 发热 (疫苗组10.3 % ，对照组8.6 %),恶心(疫苗组4.2 %， 对照组4.1%), 瘙痒 (疫苗组3.1%，对照组2.8%) 和头晕 (疫苗组2.8 %，对照组2.6 %).
Dosage and administration for GARDASIL
GARDASIL剂量和用法
GARDASIL is a ready-to-use, three-dose, intramuscular vaccine. GARDASIL should be administered in three separate intramuscular injections in the upper arm or upper anterior thigh over a six-month period. The following dosage schedule is recommended: first dose at elected date, second dose two months after the first dose and the third dose six months after the first dose.
GARDASIL是种随时可用的、三次肌肉注射的疫苗，GARDASIL应该在六个月内分三次在上臂或其它部位注射。推荐以下的给药日程：某天进行首次注射，在首次注射两个月后再次注射，首次注射后六个月第三次给药。
GARDASIL is widely available throughout the United States
GARDASIL在全美广泛使用
There is broad private and public health insurance coverage for GARDASIL. Health plans covering approximately 98 percent of privately insured lives in the U.S. (currently more than 140 insurance plans) have implemented coverage for GARDASIL; however, individual benefit coverage and rates provided by health plans may vary.
GARDASIL有广泛的个人和公共卫生保险。美国覆盖98%的个人保户生活的健康计划（目前已超过140种保险计划）也将GARDASIL纳入保险范围，但是，个人在健康计划中的受益范围和程度会有所变化。
GARDASIL was also added to the Vaccines for Children (VFC) Program on November 1, 2006, providing coverage for many who do not have private health insurance. All of the 55 immunization projects in the U.S. have adopted GARDASIL and most are filling provider orders.
GARDASIL也于2006年11月1日起加入儿童疫苗接种项目，为那些没有个人健康保险的儿童提供疫苗。美国55个免疫接种计划都接受了GARDASIL，其中大多数填满订单。
Merck has also initiated a new patient assistance program for vaccines. Through this program, currently available in private physicians' offices and private clinics, Merck is making available, free of charge, GARDASIL and other Merck vaccines indicated for use in individuals ages 19 and older who are uninsured and who are unable to afford vaccines.
默克还启动了一个新的援助患者疫苗项目。通过这个项目，默克将目前仅在医生和诊所提供的疫苗免费供应给那些19岁及以上的没有保险和负担不起疫苗的个人，包括GARDASIL和默克的其他种疫苗。
GARDASIL is approved in 70 countries
GARDASIL已在70个国家和地区获得批准
GARDASIL (sold in some countries as SILGARD® has been approved in 70 countries, including the United States, the 27 countries of the European Union, Mexico, Australia, Taiwan, Canada, New Zealand and Brazil, and additional applications are currently under review with regulatory agencies in many more countries around the world.
GARDASIL（在某些国家称为SILGARD®）已在70个国家和地区获得批准，包括美国、欧盟27国、墨西哥、澳大利亚、台湾、加拿大、纽西兰和巴西，同时其他的申请正在全球更多国家代理商考察中。
Merck will donate free vaccine to the non-profit organization PATH to support demonstration studies designed to accelerate the availability of cervical cancer vaccines in the most impoverished nations. PATH is funded by a grant from the Bill & Melinda Gates Foundation. Merck is also working with India's Council of Medical Research to study GARDASIL in India. Merck will make its new vaccines, including GARDASIL, available to developing world countries at dramatically lower prices.
默克将捐赠免费疫苗给非营利组织——帕斯适宜卫生科技组织（PATH），PATH是由Bill & Melinda Gates基金资助的。默克还正在与印度医学研究委员会合作研究GARDASIL在印度的使用。默克将把它的新疫苗包括GARDASIL以尽可能低的价格提供给发展中国家。
HPV is a common infection
HPV是一个常见的感染
In the United States, approximately 20 million people are infected with HPV, and approximately 80 percent of females will have acquired HPV by age 50. For most people, HPV goes away on its own; however in some, certain high-risk types of HPV, if unrecognized and untreated, can lead to cervical cancer. Cervical cancer is the second most common cause of cancer death in women worldwide, resulting in nearly a half-million diagnoses and 240,000 deaths each year. It is estimated that in 2007, there will be approximately 11,150 new cases of cervical cancer and 3,700 deaths in the United States. Approximately 6,000 cases of vulvar or vaginal cancer are diagnosed annually in the U.S.
在美国，大约有两千万人感染了HPV，到50岁时有80%的妇女感染过HPV。对大多数人来说，HPV感染可以自愈，但是对于某些人，某种高危型的HPV感染——如果没有发现也未处理的话——能导致子宫颈癌。子宫颈癌是世界上女性肿瘤中第二大死因，每年有接近50万新增病例，同时有24万死于宫颈癌。据估计，2007年美国将有11150个新增病例和3700死亡案例。在美国每年大约有6000名阴道癌或外阴癌被确诊。
Certain low-risk types of HPV cause genital warts and can lead to abnormal Pap results. Approximately one million cases of genital warts occur each year in the United States and an estimated 32 million cases occur worldwide. Additionally, there are an estimated 4.7 million abnormal Pap results that require follow-up each year in the United States. At least 3 million of these results are caused by some type of HPV.
某些低危的HPV型可引起生殖器疣并导致异常的巴氏试验结果。每年美国大约有一百万的生殖器疣病例，全球大概有三千两百万病例。另外，在美国每年大约有四百三十万巴氏试验异常者需要随访，至少其中的三百万是某种亚型的HPV引起的。
Other Information about GARDASIL
关于GARDASIL的其他信息
In 1995, Merck entered into a license agreement and research collaboration with CSL Limited of Australia relating to technology used in GARDASIL. GARDASIL also is the subject of other third-party licensing agreements.
1995年，默克签署了许可证协议，与CSL Limited of Australia在GARDASIL使用相关技术方面进行合作。默克也是其他第三方许可证协议的主体。
Merck recently announced that it submitted a supplemental Biologics License Application (sBLA) to the FDA that includes efficacy data showing GARDASIL offers some protection against additional cervical cancer causing HPV types responsible for greater than 10 percent of cervical cancers, data on protection against additional gynecological cancers -- vaginal and vulvar -- and data on immune memory.
最近，默克宣布他向美国食品和药品管理局递交了生物许可证申请的补充文件，其中包括证明GARDASI对引起10%以上子宫颈癌的HPV亚型导致的其它宫颈癌有一定保护作用的数据，对其它妇科肿瘤（阴道癌和外阴癌）有预防作用的数据以及对免疫记忆细胞作用的数据。
Source: Merck
来源：默克
Merck声明
2007年5月9日下午 6:24
《新英格兰医学杂志》公布默克公司子宫颈癌疫苗GARDASIL®的最新结果
2007年5月9日WHITEHOUSE STATION, N.J.报道 2007年5月9日《新英格兰医学杂志》发表了默克公司子宫颈癌疫苗GARDASI（人乳头瘤病毒 6、11、16、18型四联重组疫苗）的两个临床3期结果。第一个结果，GARDASIL对GARDASIL所针对的四种人乳头瘤病毒引起的宫颈、阴道和外阴疾病有100%的保护作用。第二个研究表明GARDASIL对于两种主要的致癌型病毒HPV 16 和HPV18引起的子宫颈癌前病变进展有98%的防护作用。这些研究结果是在15到26岁女性中获得的，她们在研究开始时并未感染相关的人乳头瘤病毒，研究持续了3年，其中包括由于向美国食品和药品管理局提交数据申请获批而增加的1年随访期。亚特兰大艾莫雷大学医学院妇产科妇科肿瘤学副教授、医学博士Kevin Ault说：“在这两项研究中，GARDASIL在先前未接触过疫苗针对的几种HPV亚型的妇女中显示出明显的预防严重HPV相关疾病的能力，包括高度恶性子宫颈癌前病变。在11到26岁的女性中广泛的免疫接种GARDASIL，同时不断筛查，能减少子宫颈癌和其他HPV相关疾病的发病。” 据估计，2007年美国的子宫颈癌患者将会超过11000人，全球将有将近500000患者。GARDASIL有助于预防四种HPV亚型引起的疾病，这四种HPV（HPV6, 11, 16 和18型）引发的疾病占HPV引发疾病的大多数，包括70%的子宫颈癌和90%的生殖器疣。而且都可导致巴氏试验异常和低度恶性的宫颈损伤。默克实验室生物制品临床研究执行主任和HPV疫苗项目主管Eliav Barr博士说：“我的各国同事对这个结果感到非常自豪，他们为探知GARDASIL对HPV 6, 11, 16,和18型引起的宫颈、外阴和阴道疾病发病危险的影响做出了巨大的贡献。在那些未感染GARDASIL所针对的这四种HPV的妇女中，GARDASIL减少了由这四种病毒引发的宫颈疾病。同时，在更大样本的群体中，GARDASIL不仅降低了疫苗所针对的HPV病毒导致的宫颈、外阴和阴道疾病，而且还减少了其他类型HPV引发的宫颈、外阴和阴道疾病。” GARDASIL于2006年6月8日被美国食品和药品管理局批准，同时美国疾病控制中心和免疫接种顾问委员会推荐11到26岁的女性使用这种疫苗。研究表明GARDASIL可以预防HPV16和18型相关的子宫颈癌、非侵入性宫颈癌（宫颈上皮瘤样病变样病变(CIN)3级和原位腺癌(AIS)）、宫颈癌前病变（宫颈上皮瘤样病变(CIN)2级）、外阴癌前病变（外阴上皮瘤样病变样病变(VIN) 2/3级）和阴道癌前病变（阴道上皮瘤样病变(VaIN) 2/3级），同时对于HPV6、11、16和18型引起的生殖器疣和低度恶性的宫颈损伤(CIN 1级)具有保护作用。GARDASIL禁用于对疫苗活性成分或佐剂过敏者。
对CIN 2/3（最有意义的指标）效用的研究
研究中的FUTURE I 和 FUTURE II是在29个国家进行的前瞻性的、双盲的、安慰剂对照的随机试验。参与者是年龄在15到26岁之间的女性，她们分别在第一天、两个月、六个月接受了共3次的GARDASIL或安慰剂注射。研究主要分析GARDASIL与安慰剂相比的有效性，所有的受试者在研究初期均未感染过这四种HPV(6, 11, 16 和/或18型)，而且在7个月中保持未被感染，并在一年内完成GARDASIL的三次剂量，没有违反实验设计。FUTURE I评估GARDASIL对疫苗针对的四种HPV所致的宫颈损伤和癌前病变(宫颈上皮瘤样病变 1-3级)、外阴和阴道损伤和癌前病变（外阴上皮瘤样病变1-3级和阴道上皮瘤样病变1-3级）以及生殖器疣的发病率的影响。FUTURE II 主要是评价GARDASIL对HPV 16 和 18导致的癌前期和非侵入性癌(宫颈上皮瘤样病变 2/3级, 原位腺癌)的影响。美国食品和药品管理局和世界卫生组织将能够阻止高度恶性癌前期病变(宫颈上皮瘤样病变 2/3级, 原位腺癌)进展作为子宫颈癌疫苗有效的最有意义的指征。结果表明GARDASIL对未感染过这几种病毒亚型的女性有明显的保护作用。FUTURE I中，平均三年的随访期后，GARDASIL显示了100%的预防HPV 6-, 11-, 16- 和18相关的外阴上皮瘤样病变（VIN 1-3）、阴道上皮瘤样病变( VaIN 1-3)和生殖器疣等疾病的效果：在2261名的疫苗组中没有1例患者出现，而安慰剂对照组中的2279例中出现了60个病例。GARDASIL对于预防HPV 6-, 11-, 16-, 和18相关的宫颈上皮瘤样病变（CIN 1-3）也是100%的有效：2241人接受疫苗后无一人发病，而2258名对照组中则有65名患者。FUTURE II中，平均三年随访期后，GARDASIL 预防HPV 16和HPV18型相关的高度恶性癌前期病变的有效率达到98%：5305名疫苗组中仅发现1位宫颈上皮瘤样病变3级患者，对照组（5260人）中有42例。
评价GARDASIL在普通女性群体中有效性的研究
研究也评估了GARDASIL在普通女性群体中的有效性，这个群体包括在实验开始时即已感染了HPV和可能患有HPV相关疾病的人。在FUTURE I，GARDASIL降低了宫颈损伤20%：疫苗组2723例中观察到344个病例，对照组2732人中有421病例；降低外阴和阴道损伤和生殖器疣34%：疫苗组2723例中104例，对照组2732例中有157例。在FUTURE II中，接种GARDASIL减少宫颈上皮瘤样病变2/3级和原位腺癌发生率17%：疫苗组6087例中有219例，对照组6080例中有266例。这两个研究中，大多数损伤发生在那些研究初期即已感染了HPV的女性中。接种GARDASIL并不能改变已感染患者的病程，疫苗接种时即已感染病毒是随访早期大多数损伤的病因，但是，三年后，疫苗的作用开始变得明显，此时由新感染疫苗HPV型所致的损伤只在对照组出现，在疫苗组并未发现。这两个研究中，观察到的副作用和先前的报道是相似的。
关于GARDASIL的其他重要信息
保健师应该告知患者、父母或监护人，疫苗并不能取代常规的子宫颈癌筛查。接受GARDASIL的女性应该按照护理标准继续接受子宫颈癌筛查。GARDASIL接种可能并不是对所有的接种者都有效，它也不能用于治疗生殖器疣、子宫颈癌、子宫颈上皮瘤样病变、外阴上皮瘤样病变和阴道上皮瘤样病变。同时对于其他类型HPV感染引起的疾病GARDASIL没有预防作用。在GARDASIL的临床研究中，疫苗副作用发生率至少为1%，比安慰剂对照组的稍高，副作用主要是疼痛 (疫苗组83.9 %，对照组 75.4 %), 肿胀(疫苗组25.4 %，对照组15.8 %), 红斑(疫苗组24.6%， 对照组18.4 %), 发热 (疫苗组10.3 % ，对照组8.6 %),恶心(疫苗组4.2 %， 对照组4.1%), 瘙痒 (疫苗组3.1%，对照组2.8%) 和头晕 (疫苗组2.8 %，对照组2.6 %).
GARDASIL剂量和用法
GARDASIL是种随时可用的、三次肌肉注射的疫苗，GARDASIL应该在六个月内分三次在上臂或其它部位注射。推荐以下的给药日程：某天进行首次注射，在首次注射两个月后再次注射，首次注射后六个月第三次给药。
GARDASIL在全美广泛使用
GARDASIL有广泛的个人和公共卫生保险。美国覆盖98%的个人保户生活的健康计划（目前已超过140种保险计划）也将GARDASIL纳入保险范围，但是，个人在健康计划中的受益范围和程度会有所变化。GARDASIL也于2006年11月1日起加入儿童疫苗接种项目，为那些没有个人健康保险的儿童提供疫苗。美国55个免疫接种计划都接受了GARDASIL，其中大多数填满订单。默克还启动了一个新的援助患者疫苗项目。通过这个项目，默克将目前仅在医生和诊所提供的疫苗免费供应给那些19岁及以上的没有保险和负担不起疫苗的个人，包括GARDASIL和默克的其他种疫苗。
GARDASIL已在70个国家和地区获得批准
GARDASIL（在某些国家称为SILGARD®）已在70个国家和地区获得批准，包括美国、欧盟27国、墨西哥、澳大利亚、台湾、加拿大、纽西兰和巴西，同时其他的申请正在全球更多国家代理商考察中。默克将捐赠免费疫苗给非营利组织——帕斯适宜卫生科技组织（PATH），PATH是由Bill & Melinda Gates基金资助的。默克还正在与印度医学研究委员会合作研究GARDASIL在印度的使用。默克将把它的新疫苗包括GARDASIL以尽可能低的价格提供给发展中国家。
HPV是一个常见的感染
在美国，大约有两千万人感染了HPV，到50岁时有80%的妇女感染过HPV。对大多数人来说，HPV感染可以自愈，但是对于某些人，某种高危型的HPV感染——如果没有发现也未处理的话——能导致子宫颈癌。子宫颈癌是世界上女性肿瘤中第二大死因，每年有接近50万新增病例，同时有24万死于宫颈癌。据估计，2007年美国将有11150个新增病例和3700死亡案例。在美国每年大约有6000名阴道癌或外阴癌被确诊。某些低危的HPV型可引起生殖器疣并导致异常的巴氏试验结果。每年美国大约有一百万的生殖器疣病例，全球大概有三千两百万病例。另外，在美国每年大约有四百三十万巴氏试验异常者需要随访，至少其中的三百万是某种亚型的HPV引起的。
关于GARDASIL的其他信息
1995年，默克签署了许可证协议，与CSL Limited of Australia在GARDASIL使用相关技术方面进行合作。默克也是其他第三方许可证协议的主体。最近，默克宣布他向美国食品和药品管理局递交了生物许可证申请的补充文件，其中包括证明GARDASI对引起10%以上子宫颈癌的HPV亚型导致的其它宫颈癌有一定保护作用的数据，对其它妇科肿瘤（阴道癌和外阴癌）有预防作用的数据以及对免疫记忆细胞作用的数据。
来源：默克
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