A long-term follow-up study shows the sustained efficacy, immunogenicity, and safety of GlaxoSmithKline’s human papillomavirus (HPV) vaccine Cervarix. Women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine were followed for more than 9 years, and vaccine efficacy (VE) against incident infection was 100%. This is the longest follow-up report for a licensed HPV vaccine.
Persistent infection with HPV has been clearly established as the necessary cause of the overwhelming majority of cervical cancer cases. At least 40 different HPV types are known to infect the genital mucosa, of which approximately 15 are associated with cervical cancer. Among these types, HPV-16 and HPV-18 are the most common and responsible for approximately 70% of cervical cancers. Both HPV-16 and HPV-18 are included in the two licensed HPV vaccines (GSK’s Cervarix and Merck’s Gardasil), which are now widely available and used.
Evidence of long-term efficacy against vaccine HPV-types is very important, particularly with respect to maintaining public confidence in mass vaccination programs. HPV vaccines initially were recommended for young girls and women age 9 to 25 years who have not been exposed to HPV. Since HPV causes not only cervical cancer but also genital warts and anal cancer, HPV vaccines are also recommended for boys in many countries.
For this study, participants of previous studies from Brazil were invited to continue follow-up, and 437 women from five centers participated in this 36-month long-term follow-up for 113 months (9.4 years). The study was published in Human Vaccines & Immunotherapeutics (2014;10).
During this study, no new HPV-16/18-associated infections or cyto-histopathologic abnormalities occurred in the vaccine group. In particular, VE against HPV-16/18 incident infection was 100%. VE was 95.6% against incident infection over 9.4 years. No cases of either 6- or 12-month HPV-16/18 persistent infection were found in the vaccine group, versus four cases and one case, respectively, in the placebo group during the 26-months follow-up.
VE was 97.1% against atypical squamous cells of undetermined significance (ASC-US), 95% against low-grade squamous intraepithelial lesion (LISL), and 100% against cervical intraepithelial neoplasia grade 1 (CIN1+) and grade 2 (CIN2+) associated with HPV-16/18.
All vaccines remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. High and sustained levels of IgG antibodies were observed, reaching a plateau approximately 18 months after the first vaccine dose and remaining stable thereafter. Compared with levels following natural infection, IgG levels in the vaccine group were 10.8-fold and 10.0-fold higher for HPV-16 and HPV-18, respectively.
“HPV vaccine has been distinctive in having achieved 100% protective efficacy in licensure trials and showing excellent persistence of protective immunity. The data in this article show persistence of protection for about one decade, which should give adolescents and young adults an increased level of confidence in taking this vaccine and being protected against the development of cervical and other cancers,” said Ronald Ellis, MD, who is editor-in-chief of Human Vaccines & Immunotherapeutics.