Reductions in Certain Types of HPV-Related Cervical and Non-Cervical Diseases in Women and Men Observed with Real-World Use of Merck's GARDASIL® in Systematic Literature Review of 138 Studies
November 07, 2022 at 06:45 AM EST
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that an updated systematic literature review examining the global impact and effectiveness of HPV vaccination using GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] was published online in the journal Expert Review of Vaccines. This systematic review observed that use of GARDASIL led to reductions in the rates of high-grade (precancerous) and low-grade cervical lesions, as well as reductions in certain non-cervical HPV-related diseases and HPV infection in women and men. The systematic review included 138 peer-reviewed studies, published between March 1, 2016, and March 31, 2020. It details the impact and effectiveness of GARDASIL through immunization programs in 23 countries, across Africa, Asia, Europe, Australia, South America and North America and builds on a prior review of real-world data published in 2016. The previous real-world analysis was based on 58 peer-reviewed studies published between Jan. 1, 2007, and Feb. 29, 2016, across Australia/New Zealand, Europe and North America. Studies examining GARDASIL 9® (Human Papillomavirus 9-valent Vaccine, Recombinant) were not included in this review.
In the U.S., GARDASIL1 is indicated for use in females 9 through 26 years of age for the prevention of cervical, vulvar, vaginal and anal cancers caused by HPV types 16 and 18; genital warts caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18. GARDASIL is also approved for use in males 9 through 26 years of age for the prevention of anal cancer caused by HPV types 16 and 18, for the prevention of anal dysplasia and precancerous lesions caused by HPV types 6, 11, 16 and 18, and for the prevention of genital warts caused by HPV types 6 and 11. GARDASIL is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL.
“Since its first authorization in 2006, GARDASIL has been widely used in national immunization programs all around the world, which has enabled researchers to study the impact of HPV vaccination in a broad range of populations and settings,” said Ravinder Dhawan, vice president, head of center for observational and real-world evidence, Merck Research Laboratories. “These real-world data from more than one hundred published studies show decreases in vaccine-type HPV infections and related diseases and are an important reminder that we need to do more to expand vaccination to males and females as part of the global fight to lessen the incidence of certain HPV-related diseases and cancers.”
1 GARDASIL is no longer marketed in the United States. GARDASIL 9 was approved in the United States in 2014.
In addition to the inclusion of real-world data from more countries compared to the previous review published in 2016, longer-term effects of HPV vaccination were also observed, including reductions in certain types of cervical high-grade (precancerous) lesions. Studies included in this review reported reductions in vaccine-targeted low-grade and high grade (precancerous) cervical lesions in females. The greatest reductions were observed in younger age groups (14-17 years), with up to 73 percent reduction in CIN3+ (cervical pre-cancerous lesions) among vaccinated females. Consistent with the previous review, declines in the incidence of anogenital warts continue to be observed within vaccine-targeted female age groups, with larger decreases (up to 88%) observed in younger age groups.
Sixteen studies reporting on non-cervical disease endpoints were also evaluated in this review. There is no routinely recommended screening for the detection of non-cervical HPV-related diseases and cancers. Findings in non-cervical disease included:
About the systematic review
Indication for GARDASIL and GARDASIL 9
The GARDASIL 9 oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Indication - Limitations of Use
GARDASIL 9 and GARDASIL do not eliminate the necessity for vaccine recipients to undergo screening for cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers as recommended by a health care provider.
GARDASIL 9 and GARDASIL have not been demonstrated to provide protection against diseases caused by:
Not all vulvar, vaginal, anal, oropharyngeal and other head and neck cancers are caused by HPV, and GARDASIL 9 and GARDASIL protect only against those vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types contained in the vaccines.
GARDASIL 9 and GARDASIL are not a treatment for external genital lesions; cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).
Vaccination with GARDASIL 9 or GARDASIL may not result in protection in all vaccine recipients.
Select Safety Information
Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following HPV vaccination. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion.
Safety and effectiveness of GARDASIL 9 and GARDASIL have not been established in pregnant women.
For GARDASIL 9, the most common (≥10%) local and systemic adverse reactions in females were: injection-site pain, swelling, erythema, and headache. The most common (≥10%) local and systemic reactions in males were injection-site pain, swelling, and erythema. For GARDASIL, the most common (≥1.0%) adverse reactions were headache, fever, nausea, dizziness; and injection-site pain, swelling, erythema, pruritus, and bruising.
The duration of immunity of GARDASIL 9 or GARDASIL has not been established.
Dosage and Administration
Administer either GARDASIL 9 or GARDASIL intramuscularly in the deltoid or anterolateral area of the thigh.
For GARDASIL 9, a complete vaccination regimen consists of:
For GARDASIL, a complete vaccination regimen for individuals 9 through 26 years of age consists of 3 doses at the following schedule: 0, 2 months, 6 months.
Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2021 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] at https://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf and Patient Information/Medication Guide for GARDASIL at https://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_ppi.pdf.
Please see Prescribing Information for GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) at https://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf and Patient Information/Medication Guide for GARDASIL 9 at https://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_ppi.pdf