Evaluation of Concomitant Human Papillomavirus Vaccination and Screening for Accelerated Elimination of HPV Infection and Cervical Cancer in Swedish Women Aged 23-25

The primary objective of this study is to evaluate whether organized, concomitant **HPV vaccination** and HPV screening, as offered by the Swedish cervical screening program to all resident women aged 23-25, will result in a more rapid elimination of HPV infection in Sweden. This objective is assessed at the population level, aiming to address the public health challenge posed by HPV infection and its related diseases, such as cervical intraepithelial neoplasia grade 2 and 3, and cervical cancer.

Secondary objectives include:

• Assessing the protection offered by Gardasil 9 against HPV infection and cervical intraepithelial neoplasia grade 2 or higher (CIN2+) by the vaccine types, evaluating the effectiveness of one-dose vaccination, and determining the effect of two-dose vaccinations.
• Measuring efficiency by the yield of histopathologically confirmed high-grade cervical cancer precursors or cancer in relation to resource consumption and convenience for women.
• Evaluating safety by monitoring the occurrence of obstetrical complications, such as preterm births, and measuring the number of excised cervical specimens found to be histopathologically benign.

The clinical trial involves a study population consisting of **female** participants aged 23 to 25 years, who are residents of Sweden. The trial focuses on evaluating the impact of organized, concomitant **HPV vaccination** and screening within the Swedish cervical screening program. Participants are selected based on their eligibility for invitation to organized cervical cancer screening and their consent to participate. The study does not include male subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The primary medical conditions of interest include **HPV infection** and related diseases, such as cervical intraepithelial neoplasia grade 2 and 3, and cervical cancer.

The clinical trial is designed to evaluate the impact of **concomitant HPV vaccination** and screening on the rapid elimination of **HPV infection** and related diseases, such as cervical intraepithelial neoplasia and cervical cancer, in Sweden. This study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. The trial is expected to span from April 2021 to December 2027, with participant involvement lasting up to 42 months. The primary endpoint is the uptake of the HPV vaccine among eligible women, while secondary endpoints include compliance with the vaccine administration schedule.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age (23-25 years) and consent to participate. Follow-up visits will be scheduled to monitor vaccine uptake and compliance, as well as to conduct HPV screenings. The end-of-study visit will assess the overall impact of the intervention on HPV infection rates. Participants may be terminated early from the study if they withdraw consent or if any exclusion criteria are met during the trial period.

The clinical trial involves the administration of **Gardasil 9**, a **Human Papillomavirus (HPV) 9-valent Vaccine (Recombinant, adsorbed)**, formulated as a suspension for injection in a pre-filled syringe. This vaccine is designed to protect against nine types of HPV, specifically types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The active substances in the vaccine are virus-like particles of the L1 protein from each HPV type, produced in yeast cells (**Saccharomyces cerevisiae** strain 1895) using recombinant DNA technology. The vaccine is administered via the **intramuscular route**. The dosing schedule allows for a maximum daily dose of one injection, with a total of two doses administered over a maximum treatment period of 42 days.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the Gardasil 9 vaccine. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol. The trial aims to evaluate the effectiveness of the vaccine in conjunction with HPV screening to achieve rapid elimination of HPV infection and reduce the incidence of cervical cancer in the target population.

Efficacy in the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the uptake of the **HPV vaccine** in eligible women, categorized by county and age strata. This will provide insights into the vaccination coverage achieved through the intervention. The secondary endpoint focuses on compliance with the HPV vaccine administration schedule, which will help determine adherence to the recommended vaccination protocol.