Reductions in certain types of HPV-related cervical and non-cervical diseases in women and men observed with real-world use of Gardasil in systematic literature review of 138 studies

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., Gardasil 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, Gaddasil 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.”

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: i.Consistent decreases observed in vaccine-type HPV infection rates in females among age groups targeted by national immunization programs, of up to 96%. ii. A consistent overall decrease in prevalence of anal infection in men was reported with variability observed by HPV-type. A significant reduction in high-grade anal pre-cancers (AIN) was observed among vaccinated versus unvaccinated men who have sex with men in one study. In years one and two after vaccination, statistical significance in the estimate was observed (HR 0.42 [95% CI: 0.22-0.82, p=0.01] and HR 0.50 [95% CI: 0.26-0.98, p=0.05], respectively). Year three results were not significant, potentially due to loss of follow-up participants in the longer-term study.

About the systematic review :A 2016 review of real-world data previously captured both the effectiveness and impact data of Gardsil since 2007-2016. This updated systematic literature review identified studies published from March 2016 through March 2020 that met the pre-specified criteria for assessment of the real-world impact of HPV vaccination on HPV-related precancerous and dysplastic cervical lesions, genital warts and HPV infection. The literature search was expanded to include peer-reviewed observational studies between January 2007 and March 2020 on additional endpoints of oral and anal HPV infections, oropharyngeal and anal lesions and recurrent respiratory papillomatosis (RRP). The review identified 138 studies from 23 countries with varying degrees of HPV vaccination coverage, among populations of different ages and used different study methods and disease endpoints. A majority of the countries used Gardasil; some countries utilized the bivalent HPV vaccine in addition to Gardasil Studies reporting only on the bivalent HPV vaccine were excluded.

See-"Real-world impact and effectiveness of the quadrivalent HPV vaccine: an updated systematic literature review"- Wei (Vivian) Wang,Smita Kothari,Jozica Skufca, Anna R. Giuliano, Karin Sundström,Mari Nygård. Received 13 Jun 2022, Accepted 23 Sep 2022, Published online: 04 Nov 2022 Download citation https://doi.org/10.1080/14760584.2022.2129615.