Gardasil has become the second best selling human vaccine with sales of over $ 1.61 billion in the year 2009. The approval and launch of the vaccine in 2006 by the FDA and EMEA resulted in strong demand due to the unmet medical need. With efficacy of over 95% in clinical trials and low prices for poor developing countries and patients, it is cost effective prevention of the HPV related cancer and genital warts. The price of the 3 dose vaccine is $300-500 in Western countries and has been offered at $ 6 in developing countries in partnership with GAVI and UNICEF. The FDA experts and its advisory panel on Vaccines have endorsed the use of Gardasil for prevention of anal cancer in adults. FDA has approved Gardasil for prevention of cervical, vulvar and vaginal cancer in females 9-26 years of age and for the prevention of genital warts and anal cancer in both females and males. The FDA rejected its use in older women 27-45 years of age due to lack of supporting data.
|Harald zur Hausen|
|Born||March 11, 1936 (age 73)
|Institutions||German Cancer Research Center|
|Known for||Discovery that HPV can causecervical cancer|
|Notable awards||2008 Nobel Prize in Physiology or Medicine|
The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine for 2008 with one half to
Harald zur Hausen
for his discovery of “human papilloma viruses causing cervical cancer”
and the other half jointly to
Françoise Barré-Sinoussi and Luc Montagnier
for their discovery of “human immunodeficiency virus”
Distribution of cervical cancer
The global public health burden attributable to human papilloma virus is considerable. More than 5% of all cancers worldwide are caused by persistent infection with this virus. Infection by the human papilloma virus is the most common sexually transmitted agent, afflicting 50-80% of the population. The Nobel Laureate
Proper Name: Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant
- Prevention of vulvar and vaginal cancer
- Vaccination in females 9 to 26 years of age for prevention of the following diseases caused by Human Papillomavirus (HPV) Types 6, 11, 16, and 18:
- Cervical cancer
- Genital warts (condyloma acuminata) and the following precancerous or dysplastic lesions:
- Cervical adenocarcinoma in situ (AIS)
- Cervical intraepithelial neoplasia (CIN) grade 2 and grade 3
- Vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3
- Vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3
- Cervical intraepithelial neoplasia (CIN) grade 1
- Vaccination in boys and men 9 through 26 years of age for the prevention of genital warts caused by HPV types 6 and 11
WebMD - Daniel J. DeNoon - 4 hours ago
Dec. 22, 2010 — The FDA today approved Merck’s Gardasil HPV vaccine for prevention of anal cancer in both males and females ages 9 through 26 years.
Vaccine approved for anal cancer prevention Los Angeles Times
USA Today - Kathleen Doheny - 15 hours ago
A test that detects the two strains of human papillomavirus (HPV) that are most likely to raise the risk of invasive cervical cancer, when combined with the Pap test, may be more accurate for many women than the Pap test …
Dalya Guris, MD, MPH
Efficacy of Gardasil
The vaccine was 89% effective in preventing HPV- types 6 and 11 infections in young males 16-26 age group. The study was done in 4000 males in 18 countries with a control group without vaccine.
|Feb. 02, 2011||New England Journal of Medicine Publishes Efficacy and Safety Data for GARDASIL® in Males|
Safety of Gardasil
Based on the review of available information by EMEA, FDA and CDC in 2009, Gardasil continues to be safe and effective, and its benefits continue to outweigh its risks.
CDC/ECDC have not changed its recommendations for use of Gardasil. FDA/EMEA have not made any changes to the prescribing information for how the vaccine is used. In addition, FDA/EMEA routinely reviews manufacturing information, and have not identified any issues affecting the safety, purity and potency of Gardasil.
Gardasil Vaccine Safety
Information from FDA And CDC on the Safety of Gardasil Vaccine
August 20, 2009
Monitoring the Safety of Gardasil
FDA and CDC closely monitor the safety of all vaccines through the Vaccine Adverse Event Reporting System (VAERS). VAERS receives unconfirmed reports of possible side effects following the use of Gardasil and all vaccines licensed in the U.S. VAERS reports are regularly reviewed for safety concerns or trends of adverse events (possible side effects).
Vaccines are manufactured in batches called lots. All vaccine lots are routinely tested and must pass all tests before they can be used, and vaccine manufacturers must comply with strict manufacturing standards. FDA also analyzes adverse events (possible side effects) associated with individual lots to look for any unusual patterns. No such patterns have been observed in FDA’s review of HPV vaccine lots since the vaccine was licensed.
In addition to VAERS, CDC has two other systems in place to monitor the safety of all licensed vaccines. The Vaccine Safety Datalink (VSD) Project is a collaborative effort between CDC and eight managed care organizations that monitors vaccine safety and addresses the gaps in scientific knowledge about rare and serious side effects following immunization. The Clinical Immunization Safety Assessment (CISA) Network is a collaboration with six academic centers in the United States to conduct clinical research on vaccine-associated adverse events.
Adverse Event Reports following Gardasil
Given the million of doses distributed, it is expected that, by chance alone, serious adverse events and some deaths will be reported in this large population during the time period following vaccinations.
On August 19, 2009, the Journal of the American Medical Association (JAMA) published an article coauthored by FDA and CDC that reviews the safety data for Gardasil for select adverse events that have been reported to VAERS, from the time period starting from product licensure in June 2006 through December 31, 2008 (JAMA. 2009;302(7):750-757). The article describes 12,424 reports of adverse events following Gardasil vaccination. Of these, 772 were reports of serious events (6.2% of the reports) and the remaining 11,652 (93.8%) were classified as non-serious. During this time period, the manufacturer, Merck and Co., has distributed over 23 million doses of Gardasil in the United States.
The Gardasil safety review assessed the following adverse events: local injection site reactions, syncope, dizziness, and nausea, headaches, hypersensitivity reactions, such as rashes, hives, itching, anaphylaxis, Guillain-Barré syndrome (GBS), transverse myelitis, motor neuron disease, venous thromboembolic events (VTEs), pancreatitis, autoimmune disorders, pregnancy, and deaths. All of these events are included in Gardasil’s labeling. In VAERS, a higher proportion of Gardasil reports were of syncope and VTEs compared with other vaccines. However, none of the adverse events in the safety review, including syncope and VTEs, were reported at rates (number of adverse events/number of doses distributed) greater than expected in a population of this age and gender and with other known contributing factors to these adverse events.
VAERS reports include syncope (fainting), pain at the injection site, headache, nausea and fever. Fainting is common after injections and vaccinations, especially in adolescents. Falls after syncope may sometimes cause serious injuries, such as head injuries, which can be prevented with simple steps, such as keeping the vaccinated person seated for up to 15 minutes after vaccination.
Thromboembolic disorders (blood clots) have been reported to VAERS in people who have received Gardasil. Most of these individuals had risk factors for blood clots such as use of oral contraceptives which are known to increase the risk of clotting. The JAMA article describes 56 cases, 31 of which were confirmed blood clot reports. Twenty eight reports (90%) had underlying known risk factors such as hormonal birth control, genetic clotting abnormalities, obesity, smoking, and immobility. In the CDC’s VSD, blood clots have not been found to occur more often than expected after over 450,000 doses of Gardasil.
Concerns have been raised about reports of deaths occurring in individuals after receiving Gardasil. As of December 31, 2008, 32 deaths had been reported to VAERS. There was not a common pattern to the deaths that would suggest they were caused by the vaccine. In the majority of cases with available autopsy, death certificate and medical records, the cause of death was explained by factors other than the vaccine.
Guillain-Barre Syndrome (GBS) has also been reported in individuals following vaccination with Gardasil. GBS is a rare neurological disorder that causes muscle weakness. It occurs spontaneously in unvaccinated individuals after a variety of specific infections. FDA and CDC have reviewed the reports of GBS that have been submitted to VAERS. To date, there is no evidence that Gardasil has increased the rate of GBS above that expected in the population. The data do not currently suggest an association between Gardasil and GBS.
Thus far, the VSD studies have not found safety signals or concerns for any of these events. The manufacturer has also committed to conduct a large postmarketing study to further assess the vaccine’s safety.
Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A, Izurieta HS, Ball R, Miller N, Braun MM, Markowitz LE, Iskander J.
JAMA. 2009 Aug 19;302(7):750-7.PMID: 19690307 [PubMed – indexed for MEDLINE]
Public Health Genomics. 2009;12(5-6):319-30. Epub 2009 Aug 11.PMID: 19684444 [PubMed – in process]
BMJ. 2010 Jul 20;341:c3493. doi: 10.1136/bmj.c3493.
Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.
The FUTURE I/II Study Group. PMID: 20647284 [PubMed – as supplied by publisher]
J Natl Cancer Inst. 2010 Mar 3;102(5):325-39. Epub 2010 Feb 5.
Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women.
Muñoz N, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM, Perez G, Brown DR, Koutsky LA, Tay EH, Garcia PJ, Ault KA, Garland SM, Leodolter S, Olsson SE, Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dillner J, Huh WK, Joura EA, Kurman RJ, Majewski S, Myers ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan JT, Lupinacci LC, Giacoletti KE, Sings HL, James MK, Hesley TM, Barr E, Haupt RM.
Division of Research and Public Health, National Institute of Cancer, Bogotá, Colombia . firstname.lastname@example.org
Rwanda rolls out cervical cancer vaccine for girls The Guardian - Apr 25, 2011
Rwanda is today launching a cervical cancer vaccination programme for all its 12 to 15 year-old girls – the first comprehensive national scheme in Africa, where it is so badly needed.
JAMA, June 20, 2007; 297: 2578.
Abdelmutti N, Hoffman-Goetz L.
Women Health. 2009 Jul;49(5):422-40.PMID: 19851946 [PubMed – in process]
Sales and Marketing
Marketing HPV Vaccine: Implications for Adolescent Health and Medical Professionalism
JAMA, August 19, 2009; 302: 781 – 786.
Leddy MA, Anderson BL, Gall S, Schulkin J.
J Pediatr Adolesc Gynecol. 2009 Aug;22(4):239-46.PMID: 19646670 [PubMed – indexed for MEDLINE]
GAVI takes first steps to introduce vaccines against cervical cancer and rubella. The group will buy 2 million doses of HPV vaccines from Merck and GSK. merck has offered to supply Gardasil at $15 for 3 doses for poor countries. GSK is in talks with GAVI.
November 25, 2009 (DOI: 10.1056/NEJMp0911380)
CDC Cervical Cancer Screening Slides
Gardasil versus Cervarix
Cervarix (Glaxosimthkline ) gives protection against HPV 18 and 16 but gives cross protection against viruses
31 and 45 which cause cervical cancer.
Gardasil (Merck) protects against HPV 16 , 18 , 6 , 11 in which first two cause cancer and other two cause genital warts.
Cervarix can be given to women of age group between 10-46 years whereas Gardasil can be given to younger age group between 16-25 years of age.
Cost of Cervarix is more than Gardasil.
Cervical cancer vaccine in India :
Cancer cervix :
It takes lives of 8 women in India every hour.
WHO studies show that 1.3 lakh Indian women are diagnosed with cancer cervix every year and approximately 74,000 die of this cancer every year.
Women in India have a 2.5% life time risk to get cancer cervix which is double the risk as compared to data worldwide which is 1.3%.
In majority it can be prevented by using vaccine.
Approximately 80% of women get one or more type of HPV by the age of 50.
16 and 18 HPV strains cause 70% cancer.
MSD pharma India , local affliate of Merck said that Gardasil prevents cervican cancer , cervical lesions , vulval lesions and genital warts.
Announcing the launch Dr Naveen A Rao , MD -MSD India said ” with the lauch of Gardasil we have initiated the war against cervican cancer, the number one cause of mortality in Indian women.”
Gardasil provides 98% protection against cervical precancers caused by HPV 16, 18 said Dr Neerja Bhatia from AIIMS.
MSD India is collaborating with ICMR as a public -private partnership to bring vaccine to Indian public sector at an affordable price.
IAPCOI -Indian academy of paediatrics committee of immunization recommends : This vaccine has a favorable
tolerability profile.It recommends initiation of vaccination between 10-12 years of age.Catch up vaccination is permitted up to the age of 26 years.It is given in 3 doses , 0, 2 and 6 months.
Gardasil side effects :
Fainting is common among adolescents.They should remain seated for 15 minutes.
Shot is more painful than other vaccines.
General side effects like malaise , fatigue , muscle and joint pains are common.
Contraindications : Severe allergy to yeast.
Fever more than 100 degree F.
Thanks are due to Mr. Jean-Antoine de Mandato (PDP, Geneva) for providing office facilities
- HPV Common Infection. Common Reality. - A series of brochures to help individuals and health care providers understand HPV, its prevention, and its consequences.
- Fact Sheet
- HPV and Men - CDC Fact Sheet (updated August 14, 2007)
- HPV Vaccine – Questions & Answers For The Public About the Safety and Effectiveness of the Human Papillomavirus (HPV) Vaccine (Updated July 17, 2008)
- HPV Vaccine Information for Young Women (en español) (Updated June 30, 2008)
- HPV Vaccine Information for Clinicians (en español) (Updated June 30, 2008)
- HPV Myths & Misconceptions - ASHA fact sheet debunks HPV myths. See “HPV & Cervical Cancer” below for more recent information on PAP tests.
- HPV: Genital Warts, Questions and Answers - ASHA fact sheet.
- HPV & Cancer: Q&A - NCI fact sheet.
- Human Papilloma Virus (HPV), Cancer, and HPV Vaccines – Frequently Asked Questions - from ACS.
- STD Surveillance 2007 – Other Sexually Transmitted Diseases – Human Papillomavirus
- Human papillomavirus (HPV) — Prevalence of high-risk and low-risk types among females 14 to 59 years of age reported from a national survey, 2003–2004 (Figure 43)
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- QuickStats: Prevalence of HPV Infection Among Sexually Active Females Aged 14–59 Years, by Age Group — National Health and Nutrition Examination Survey, United States, 2003–2004
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HPV & Cervical Cancer
- Common Questions about HPV and Cervical Cancer - for women who have HPV (August 27, 2007)
- Making Sense of Your Pap & HPV Test Results (9 July 2008)
- Basic Facts on Screening and the Pap Test - Cervical cancer screening information from CDC.
- Early Detection of Cervical Cancer - Information pages for patients about cervical cancer, types of screening tests, and recommendations from ACS.
- Pap Tests & Cervical Health: A Healthy Habit for You - Questions and answers about Pap tests from NCI.
- Pap Tests for Older Women - Questions and answers about Pap tests for women aged 65 years and older from NCI.
- HPV Vaccine Monitoring (7 November 2008)
- Questions and Answers about HPV Vaccine Safety
- Quadrivalent Human Papillomavirus Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP) - MMWR March 23, 2007
- CDC’s Advisory Committee Recommends Human Papillomavirus Virus Vaccination – Media advisory. (28 June 2006)
- HPV Vaccine Information for Young Women (Updated June 30, 2008)
- HPV Vaccine Information for Clinicians - (Updated June 30, 2008)
- FDA Licenses New Vaccine for Prevention of Cervical Cancer and Other Diseases in Females Caused by Human Papillomavirus - FDA media release (June 8, 2006)
- GARDASIL® Questions and Answers - Product Approval Information from FDA (June 8, 2006)
- Human Papillomavirus (HPV) Vaccine Safety
- Human Papillomavirus: HPV Information for Clinicians - Brochure on transmission, prevention, detection and clinical management of HPV. Also in Spanish (27 August 2007)
- HPV Vaccine Information for Clinicians - (Updated June 30, 2008)
- Summary Tables of Cervical Cancer Screening Guidelines and Recommendations for New Technologies - from CDC.
- Lower Genital Tract Disease Series - Six online CME courses on HPV, cervical cancer screening and management, and patient barriers to screening and follow-up from ASCCP.
- Curricula for Community-Based Workshops - from ASHA.
- Self-Study STD Modules for Clinicians - Includes HPV web-based educational module from CDC.
- STD Case Series - Continuing education for practitioners in primary health care, family medicine, emergency medicine and other specialties who provide care to persons with or at risk for sexually transmitted disease (published by the National Network of STD/HIV Prevention Training Centers). Includes HPV case.
- HPV Creative Material Testing - report, brochure and poster
- Ready-To-Use STD Curriculum - Curriculum modules for clinical educators on seven different STD topics, including HPV from CDC.
- Curricula for Community-Based Workshops - Six-session workshop series for African American and Latina women on cervical cancer, Pap-testing, follow-up care, STDs, and communication with health care providers and partners from ASHA.
- Cervical Human Papillomavirus Screening among Older Women - EID November 2005
November 16-17, 2010: Vaccines and Related Biological Products Advisory Committee
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