Gardasil (Merck) for Cervical Cancer and Genital Warts

Gardasil A quadrivalent HPV Vaccine

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Abstract

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.

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Introduction

 
According to WHO, there were 510000 cases of cervical cancer in the world resulting in 288000 deaths each year. India has a higher burden with 130000 new cases and 75000 deaths each year due to cervical cancer. India has 25% of the global cervical cervical cancer burden by number of patients and deaths.  Recent CDC data indicates that over 20 million Americans are already infected with human papilloma virus and 6.2 million new cases are detected every year. Each year 11000 cases of cervical cancer resulting in 4000 deaths in the US. Over 70 % of cervical cancer is caused by 2 strains of HPV 16 and 18 and 90% of anogenital warts are caused by 2 strains of HPV, 6 and 11, all four of these strains can be prevented by a quadrivalent vaccine Gardasil. About 1% of sexually active men have genital warts and over 10,000 women develop other types of genital cancer due to HPV infections each year. Genital contact favors HPV transmission and spreads infection. In most of the cases (70-90%) our immune system can overcome HPV infection and eliminate infected cells.

Herald zur Hausen in Heidelberg during the 1977-1980 period, first isolated the HPV type 6 in human genital warts and later detected the presence of HPV 16 in 50% of cervical cancer cells and HPV 18 in 17-20% of cancer cells. The advent of PCR  resulted in rapid detection of the HPV types in cervical cancer and so far over 106 types of viruses have been described. A pharmaceutical company turned down 
zur Hausen request to develop a vaccine in 1984. It was only in 1991 that the idea of HP virus as a leading cause of cervical vaccine was accepted and industry started development of HPV vaccine.  
Finding the viral link: the story of Harald zur Hausen
Infections Causing Human Cancer (2006) (Print ISBN 9783527310562; Online ISBN 9783527609314)

Harald zur Hausen
Born March 11, 1936 (age 73)
GelsenkirchenGermany
Nationality German
Fields Virology
Institutions German Cancer Research Center
Known for Discovery that HPV can causecervical cancer
Notable awards 2008 Nobel Prize in Physiology or Medicine

From NobelPrize.org

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

Map

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

in his recent lectures has mentioned 500000 deaths per year from cervical cancer and 21% of global cancer burden due to chronic infections. 

FDA Approves Roche’s HPV Test for Identifying Women at Highest Risk for Cervical Cancer

http://www.roche.com/media/media_releases/med-cor-2011-04-20.htm

 
Copy From NCI Visuals Online Images
Human Papilloma Virus
 
 

 

preview                

 

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   Cervarix (Glaxo Smith Kline) pour Cancer du col de l’utérus | Ipilimumab (BMS) a examen: ¿a por el cáncer?/ Le Ipilimumab (BMS): un remède magique contre le mélanome ?/



 
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Regulatory Milestones

Gardasil was approved by the FDA in June, 2006 for prevention of HPV related cancer in girls. Its European approval was in December 2006. FDA approved additional indications for prevention of vaginal and vulvar cancer in September 2008. In October 2009, FDA approved the new indication for prevention of genital warts in boys and men. CDC’s Advisory Committee on Immunization Practices (ACIP) recommended a routine 3-dose vaccination series for girls 11 and 12 years of age.  The vaccine is also recommended for girls and women ages 13 through 26 years who have not yet been vaccinated or who have not received all 3 doses.

Gardasil 

Proper Name: Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant

Merck & Co., Inc.

Prescribing Information
Patient Product Information
Product Web site

Indications:

  • 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
GARDASIL may not fully protect everyone, and does not prevent all types of cervical cancer, so it’s important to continue routine cervical cancer screenings. GARDASIL does not treat cervical cancer or genital warts. GARDASIL will not protect against diseases caused by other HPV types or against diseases not caused by HPV. GARDASIL is given as 3 injections over 6 months.

The FDA reviewers and Vaccine advisory panel have backed the use of Gardasil to prevent anal cancer in adults. This was based on a trial involving 4000 men and the vaccine had an efficacy of 75% in preventing HPV 
 related anal cancer. FDA approved the indication on 22 Dec., 2010.

Gardasil Approved for Anal Cancer Prevention 

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

Gardasil vaccine OK to prevent anal cancer, FDA says 

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 

Study: HPV Tests Better at Predicting Cervical Cancer Than Pap Tests

 WebMD


New England Journal of Medicine Publishes Additional Efficacy and Safety Data for GARDASIL® in Males

    Oct. 25, 2011

CDC Advisory Committee on Immunization Practices Votes for Expanded Use of GARDASIL®in Boys and Young Men

NCI Visuals Online Images
AV Number: AV-8000-3416
 
Pap Smear Diagnosis by Laser
 
 

 

 


A copy of selected slides presented by Merck medical team to the FDA advisory committee is presented here for information. 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM183839.ppt


Efficacy of Gardasil

Gardasil was the first human vaccine to show efficacy of almost 100% in prevention of HPV related cancer. The original NDA contained clinical trial and safety data on 26000 girls and women 9-26 years of age. Over 13000 of these received at least one or more doses of the vaccine. In clinical trials the vaccine was highly effective in preventing HPV related pre-cancer lesions in a 3 dose schedule.  

Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection.

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


Exceptional Protection


Cervical Cancer                         Vulvar/Vaginal cancer

                              Genital Warts






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.


Reproduced from 


Gardasil Vaccine Safety
Information from FDA And CDC on the Safety of Gardasil Vaccine

August 20, 2009


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.


Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine.

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]



Prevention of human papillomavirus infections and associated diseases by vaccination: a new hope for global public health.

Harper DM.

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 GroupPMID: 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 NKjaer SKSigurdsson KIversen OEHernandez-Avila MWheeler CMPerez GBrown DRKoutsky LATay EHGarcia PJAult KAGarland SMLeodolter SOlsson SETang GWFerris DGPaavonen JSteben MBosch FXDillner JHuh WKJoura EAKurman RJMajewski SMyers ERVilla LLTaddeo FJRoberts CTadesse ABryan JTLupinacci LCGiacoletti KESings HLJames MKHesley TMBarr EHaupt RM.

Division of Research and Public Health, National Institute of Cancer, Bogotá, Colombia . nubia.munoz@free.fr

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.

Confusion Over Obtaining the HPV Vaccine–An Editorial  EmpowHer


THE WORLD IN MEDICINE:
Joan Stephenson
HPV Vaccine
JAMA, June 20, 2007; 297: 2578. 

Risk Messages About HPV, Cervical Cancer, and the HPV Vaccine Gardasil: A Content Analysis of Canadian and U.S. National Newspaper Articles.

Abdelmutti N, Hoffman-Goetz L.

Women Health. 2009 Jul;49(5):422-40.PMID: 19851946 [PubMed – in process]

 

Genital Warts


Sales and Marketing

Sheila M. Rothman; David J. Rothman
Marketing HPV Vaccine: Implications for Adolescent Health and Medical Professionalism
JAMA, August 19, 2009; 302: 781 – 786. 

Obstetrician-gynecologists and the HPV vaccine: practice patterns, beliefs, and knowledge.

Leddy MA, Anderson BL, Gall S, Schulkin J.

J Pediatr Adolesc Gynecol. 2009 Aug;22(4):239-46.PMID: 19646670 [PubMed – indexed for MEDLINE]



Gardasil was the first blockbuster vaccine to have sales of over $1 billion within first full year of marketing after approval.In 2008 it was the second best selling vaccine with sales of $  2.3 billion, international sales contributing to almost 40% of the sales. Sales in 2009 were lower at $ 1.61  billion due to economic downturn, stockpiling and a weak dollar.

 

 
The vaccine can be adminstered before the young person become sexually active like vaccinate young girls and boys between the ages of 9 to 26 years. HPV vaccine is a cost effective prophylactic medical act and its use reduces harm and promotes common good amongst poor persons. It can reduce the second leading cause of cancer in women by preventing infection and HPV related cancer. The physical, phychosocial and economic burden of HPV related infection, cancer and complications is much more than the cost of vaccination for all the teenagers. It would take over a decade of vaccination to reduce the incidence and mortalility of cervical and other related cancers. HPV vaccination can prevent mobidity and mortality associated with HPV infection.
 
Opponents of the HPV vaccination campaign have included evangelics, religious right, backers of natural immunity, die hard vaccine foes and groups from right and left. It has been stated that the HPV vaccine undermines family values by promoting underage sex and sexual activity.  Moreover the vaccine may create a false sense of security from sexually transmitted diseases in innoculated persons. No data or studies are presented to back up these claims. Other stories in the media have questioned the State legislatures passing laws recommending HPV vaccination for girls and boys. Many news stories have accused the industry of turning a minor disease into a major cost item of the healthcare budget?

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.

http://www.gavialliance.org/library/news/press-releases/2011/gavi-takes-first-steps-to-introduce-vaccines-against-cervical-cancer-

 


Books and Monographs                                                                                                               

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 :

http://www.dancewithshadows.com/pillscribe/cervical-cancer-vaccine-market-hots-up-in-india-with-mercks-gardasil-and-gsks-cervarix/

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.
Pregnancy
HIV positive
Fever more than 100 degree F.




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Acknowledgements

Thanks are due to Mr. Jean-Antoine de Mandato (PDP, Geneva) for providing office facilities

and administrative support.


Krishan Maggon                                                                             
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FDA panel backs new use for Gardasil vaccine 

BusinessWeek - ‎10 hours ago‎
By AP A federal health panel says evidence supports expanding use of Merck’s Gardasil vaccine to prevent anal cancer in young men and women. 


Archive


 

November 16-17, 2010: Vaccines and Related Biological Products Advisory Committee

Krishan Maggon                                                                             

Krishan Maggon Knols  

Sources

  • American Cancer Society. Cancer Facts & Figures, 2008. Atlanta: American Cancer Society: 2008.
  • Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines 2006. MMWR 2006; 55 [No. RR-11].
  • 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(8):813-9.

  • FUTURE II Study Group. Prophylactic efficacy of a quadrivalent human papillomavirus (HPV) vaccine in women with virological evidence of HPV infection J Infect Dis. 2007; 196:1438-1446.

  • FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007; 356(19):1915-27.

  • Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al.  Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007; 356(19):1928-43.

  • Koutsky LA, Kiviat NB. Genital human papillomavirus. In: K. Holmes, P. Sparling, P. Mardh et al (eds). Sexually Transmitted Diseases, 3rd edition. New York: McGraw-Hill, 1999, p. 347-359.

  • Kiviat NB, Koutsky LA, Paavonen J. Cervical neoplasia and other STD-related genital tract neoplasias. In: K. Holmes,  P. Sparling, P. Mardh et al (eds). Sexually Transmitted Diseases, 3rd edition. New York: McGraw-Hill, 1999, p. 811-831.

  • Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER. Quadrivalent human papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2007; 56: 1-24.

  • Myers ER, McCrory DC, Nanda K, Bastian L, Matchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. American Journal of Epidemiology 2000; 151(12):1158-1171.

  • Paavonen J, Jenkins D, Bosch FX, Naud P, Salmeron J, Wheeler CM 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;370(9596):1414.

  • Weinstock H, Berman S, Cates W.  Sexually transmitted disease among American youth: Incidence and prevalence estimates, 2000.  Perspectives on Sexual and Reproductive Health 2004; 36: 6-10.

 

Peer Reviewed Published Papers

 

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