Recombinant HPV Quadrivalent (Types 6, 11, 16, and 18) Vaccine (Gardasil)

February 1, 2011

New indication: Recombinant HPV quadrivalent (types 6, 11, 16, and 18) vaccine (Gardasil) was approved for the prevention of anal cancer and associated precancerous lesions due to HPV in persons aged 9 to 26 years.

According to the American Cancer Society, there are about 5,300 people in the United States diagnosed with anal cancer each year with more women diagnosed than men. Ninety percent of these cases are associated with human papillomavirus (HPV).

Efficacy. The new indication for prevention of anal cancer and associated precancerous lesions was based upon a sub-study of a randomized, double-blind, amorphous aluminum hydroxyphosphate sulfate (AAHS)-controlled, phase 3 clinical trial that was conducted in more than 4,000 men and boys. In this sub-study, the efficacy of Gardasil against anal disease [anal intraepithelial neoplasia (AIN) and anal cancer] was evaluated in a subset of males who self-identified as having sex with other men (a population known to have a high risk and incidence of anal cancer). The vaccine (n=194) was more efficacious than placebo (n=208) in reducing the incidence of AIN grades 1, 2, and 3 related to vaccine HPV types 6, 11, 16, and 18 in those participants who were polymerase chain reaction (PCR) negative and seronegative to relevant HPV types at baseline [5 of 194 (2.6%) vs 24 of 208 (11.5%); relative efficacy: 77.5% (95% CI, 39.6%–93.3%)]. Despite this high-level of efficacy, individuals recommended for anal cancer screening by their healthcare provider should not discontinue screening even after receiving the vaccine.

Safety. The most common adverse reactions seen with this vaccine (frequency of at least 1% and greater than AAHS control or saline placebo) as part of the 6 clinical trials conducted to support all current indications were headache, fever, nausea, dizziness, and local injection site reactions such as pain, swelling, erythema, pruritus and bruising. As with other vaccines, those receiving Gardasil may develop syncope, sometimes resulting in injury due to falls. Consequently, observation for 15 minutes after each vaccine administration is recommended. Transient syncope, sometimes associated with tonic-clonic movements and other seizure-like activity (fainting, shaking, or becoming stiff), has also been reported following Gardasil administration.