Human Papillomavirus (HPV) vaccinations are designed to protect against infections caused by the human papillomavirus, a group of viruses that can infect the genital area, as well as the mouth and throat. HPV is the most common sexually transmitted infection globally. While most HPV infections resolve on their own, certain strains can persist and lead to various cancers, with cervical cancer being the most well-known.
In addition to cervical cancer, HPV is linked to other cancers, including anal and oropharyngeal (mouth and throat) cancers. The virus is responsible for a lot of these cancers, and vaccination provides a preventive measure to reduce the risk of HPV-related cancers.
The availability and widespread use of HPV vaccinations contribute to significant public health benefits by preventing infections and reducing the incidence of HPV-related cancers. Vaccination programmes are typically recommended for adolescents before they become sexually active, providing them with protection before potential exposure to the virus.
The aim of this study is to use health record data of vaccinated and unvaccinated individuals to see whether HPV vaccination reduces risk for cervical cancer in women, and anal and mouth/throat cancers in women and men. The study also aims to see whether a different number of vaccine doses (1, 2 or 3) has an effect on reducing cancer risk. This is important because if one dose provides enough protection against cancer, then vaccination programmes that currently provide three doses could be altered to reduce health service costs, whilst still providing protection against severe disease.
HPV vaccination programmes reduce not only HPV infection but also the incidence of cervical cancer. However, uncertainty remains on the real-world effectiveness of different brands, dose schedules, and their potential effect against other HPV-caused cancers.
This study aims to generate evidence from real-world data using CPRD GOLD database on the effectiveness of different doses (one, two, three) of HPV vaccination in preventing severe disease outcomes, including invasive cervical cancer, and other HPV-related cancers, for the different licensed HPV vaccines in the UK.
This will be a target trial emulation, new user matched cohort study as follows:
Eligibility criteria: Participants >9yo any date after the launch of the vaccination programme (2008)
Treatment strategies: Unvaccinated, vaccinated with 1 dose (or ≥1), vaccinated with 2 doses (or ≥2), and vaccinated with 3 doses (or ≥3).
Assignment procedures: For unvaccinated/vaccinated the unvaccinated, vaccinated are assigned as seen in the data at 15 years old. Unvaccinated will be assigned as not being vaccinated at 15 years old, and censored when (and if) they get vaccinated later on. Two or three doses will be assigned at the same moment.
Follow-up: Follow-up time starts from index date, defined as date a participant turns 15 years old. Followed until next vaccine dose or outcome event, end of available follow-up, or death of any individual of the matched pair, whichever comes first.
Statistical methods: Incidence rates and incidence rate ratios (IRR) will be calculated for outcomes at 5, 10, 15 years (if enough follow-up is available). Cox proportional hazard models will be used to calculate hazard ratios (HR) for time-to-event analyses. Negative control outcomes and empirical calibration for IRR/HR will be used to minimise residual confounding.
Analyses will be stratified by age groups of interest (age at vaccination <16, 17-19, >20 years) and sex (where applicable; i.e. objective 4).
Invasive Cervical Cancer; Cervical intraepithelial neoplasia (CIN2 and CIN3); Conization of the cervix or cold knife cone; Anal Cancer; Oropharyngeal Cancer
Albert Prats Uribe - Chief Investigator - University of Oxford
Nicola Barclay - Corresponding Applicant - University of Oxford
Antonella Delmestri - Collaborator - University of Oxford
Daniel Prieto-Alhambra - Collaborator - University of Oxford
Marta Alcalde-Herraiz - Collaborator - University of Oxford
Martí Català Sabaté - Collaborator - University of Oxford
Mike Du - Collaborator - University of Oxford
Wai Yi Man - Collaborator - University of Oxford