Long-term immunogenicity, effectiveness, and safety of nine-valent human papillomavirus vaccine in girls and boys 9 to 15 years of age: Interim analysis after 8 years of follow-up

Abstract

Background The nine-valent human papillomavirus (9vHPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The pivotal 36-month Phase III immunogenicity study of 9vHPV vaccine in 9- to 15-year-old girls and boys was extended to assess long-term immunogenicity and effectiveness through approximately 10 years after vaccination. We describe results of an interim analysis based on approximately 8 years of follow-up after vaccination. Methods Participants aged 9–15 years who received three doses of 9vHPV vaccine (at day 1, month 2, and month 6) in the base study and consented to follow-up were enrolled in the long-term follow-up study extension (N = 1272 [females, n = 971; males, n = 301]). Serum was collected at months 66 and 90 to assess antibody responses. For effectiveness analysis, genital swabs were collected (to assess HPV DNA by polymerase chain reaction [PCR]) and external genital examination was conducted (to detect external genital lesions) every 6 months starting when the participant reached 16 years of age. Cervical cytology tests were conducted annually when female participants reached 21 years of age; participants with cytological abnormalities were triaged to colposcopy based on a protocol-specified algorithm. External genital and cervical biopsies of abnormal lesions were performed, and histological diagnoses were adjudicated by a pathology panel. Specimens were tested by PCR to detect HPV DNA. Results Geometric mean titers for each 9vHPV vaccine HPV type peaked around month 7 and gradually decreased through month 90. Seropositivity rates remained >90% through month 90 for each of the 9vHPV vaccine types by HPV immunoglobulin Luminex Immunoassay. No cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or genital warts were observed in the per-protocol population (n = 1107) based on a maximum follow-up of 8.2 years (median 7.6 years) post-Dose 3. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in females and males were 49.2 and 37.3 per 10,000 person-years, respectively, which were within ranges expected in vaccinated cohorts. There were no vaccine-related SAEs or deaths during the period covered by this interim analysis. Conclusions The 9vHPV vaccine provided sustained immunogenicity and durable effectiveness through approximately 7 and 8 years, respectively, following vaccination of girls and boys aged 9–15 years.

Assessing the Long-Term Role of Vaccination against HPV after Loop Electrosurgical Excision Procedure (LEEP): A Propensity-Score Matched Comparison

“…HPV is considered the main risk factor for developing cervical cancer and other neoplastic lesions of the lower genital tract and the oropharynx [ 1 ]. Currently, several types of HPV have been identified, but only a relatively small number of these—those considered high-risk (HR)—have been recognized as a risk factor for developing pre-neoplastic and neoplastic lesions [ 2 ].…”

“…Although the prevalence of HPV is high, the proportion of patients with HPV-related lesions and cancer is relatively small. HPV persistence is the main factor influencing the risk of progression into high-grade cervical dysplasia and cancer [ 2 ].…”

Review of long-term immunogenicity following HPV vaccination: Gaps in current knowledge

“…Although various arbitrary measurement units were used, the pattern of antibody level development for all the vaccines and HPV types is comparable to the one described above. 42,[45][46][47]57,58 However, the initial decline in HPV18 following both the 4vHPV and 9vHPV vaccination seems more pronounced as measured by cLIA assay (less so in the total binding assay), which could also explain the observed faster decline in seropositivity rates. Furthermore, there were small deviations between the 4vHPV and 9vHPV vaccine that could be related to changes in the VLP concentration.…”

Warum ist die HPV-Impfung von Jungen sinnvoll?

“…Lebensjahr und bei 3 Impfungen nach dem 15. Geburtstag noch besser als bei jungen Frauen von 16-26 Jahren [12,21]. In dieser Kohorte wurde die klinische Wirksamkeit eindrucksvoll nachgewiesen [8,9].…”