Drug products: Gardasil, Silgard
ATC code: J07BM01
There are no published trials with the primary objective to assess sex differences in terms of pharmacokinetics, pharmacodynamics, and safety of vaccine against papilloma virus. No difference in effect has been demonstrated but the low number of men included in clinical trials can affect the ability to make statistically significant analysis.
Gardasil/Silgard is used in women (in Sweden) and men (in some countries) from the age of nine for prevention of precancerous anogenital (anus, cervix, vulva or vagina) lesions, cervical cancer and anal cancer caused by the two oncogenic human papillomavirus (HPV) types 16 and 18 as well as external genital warts (condyloma acuminata) caused by HPV 6 and 11 . HPV infects the squamous epithelium in men and women, causing cervical/vulvar/vaginal cancers in women, penile cancer in men as well as anogenital condyloma acuminate, oropharyngeal and anal cancers in both men and women . HPV infects the squamous epithelium in men and women, causing cervical/vulvar/vaginal cancers in women, penile cancer in men as well as anogenital condyloma acuminate, oropharyngeal and anal cancers in both men and women .
The HPV infection natural history related to age is different in men compared to women. The probability of a sexually active man acquiring a new genital HPV-infection in any given 12-month period is 0.29-0.39 per 1000 person-months, which is comparable to reported estimates for women. The rate of acquisition of new HPV-infections in men is unlike women, constant with increasing age, while it declines in women. Compared to women, older median-age at diagnosis of HPV-related cancers has been observed in men. There may be differences in the immune response to natural HPV-infection between men and women. The reported proportion of HPV seropositive men is lower than in women. Antibody titers are higher in women who are HPV seropositive and appear to provide partial protection against subsequent HPV infection, while in men antibody titers are lower and do not appear to protect against subsequent HPV infection .
No pharmacokinetics studies on the active ingredients in Gardasil/Silgard have been performed. This is in line with Note for guidance on preclinical pharmacological and toxicological testing of vaccines (CPMP/SWP/465/95) . The producer deems no dosage adjustment to be necessary according to patient's sex .
Controlled studies on differences between men and women regarding efficacy of Gardasil/Silgard are lacking. It should be noted that most studies include only women or men, respectively, and the majority of the studies have been performed in women [4-8].
Twelve clinical studies supported the licensure of Gardasil/Silgard (n=21514, 11813 on HPV vaccine, 9701 on placebo) and showed similar immunogenicity and safety profiles for women and men . The pivotal study Protocol 020 (P020) including 4055 men (3463 heterosexual men 16-23 years and 602 MSM 16-26 years) demonstrated 90.6% efficacy against external genital lesions (PIN penile/perineal/perianal cancer and genital warts caused by vaccine-matched HPV-types) in the per-protocol efficacy population (heterosexual men) . It further demonstrated 77.5% (95% CI: 39.6-93.3) efficacy against anal intra-epithelial neoplasia (AIN) and 74.9% (95% CI: 8.8-96.4) against AIN2 or worse in the MSM per protocol efficacy population including a total of 402 men .
Gardasil/Silgard has demonstrated efficacy against precancerous anal lesions (intraepithelial neoplasia grade 2 or worse) among MSM, genital warts related to HPV 6 and 11 in women and men, and medium to high grade cervical intra-epithelial neoplasia (CIN 2/3) as surrogate markers for cervical cancer, vulva (VIN 2/3) and vaginal intra-epithelial neoplasia (VaIN 2/3) in women . There is no indication that vaccine protection against anal lesions or genital warts related to HPV is sex specific . Efficacy studies were performed in women and men (16-26 years). Immune responses in boys and girls (9-15 years) were superior to those of women and men aged 16-26 years . Immune responses were similar in men and women .
The safety profile was similar in men and women .
There are no signs that hormonal contraceptives influence the effect of Gardasil/Silgard . Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).
Gardasil/Silgard should be avoided in pregnant women. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2017-01-09
Reviewed by: Mia von Euler, Expertrådet för vaccinationer
Approved by: Karin Schenck-Gustafsson