PROJECT SUMMARY Cervical cancer is the fourth most common cancer in women, contributing to about 570,000 new cases and more than 300,000 deaths in 2018, most of it occurs in the low- and middle-income countries (Bray, 2018). In Indonesia, cervical cancer is the second most prevalent type of cancer among women, with 32,000 new cases and 18,000 deaths (Global Cancer Observatory, 2019). It has been shown that human papillomavirus (HPV) infection is the major causative agent of cervical cancer (Bosch, 2002). In 2017, WHO released an HPV vaccine position paper that stated HPV vaccines should be included in national immunization programs with its primary target population is 9-14 year old girls, prior to becoming sexually active (World Health Organization, 2017). Vaccination represents the most cost-effective and efficient way for the prevention of cervical cancer caused by human papillomavirus. Currently, HPV vaccine has been introduced in nearly 100 countries globally (52%), mainly in the upper-middle- and high-income countries. However, its access in the highest burden countries (low and middle income) remains lagging. Furthermore, previous data collected by global health organizations have shown continued low compliance rates for HPV vaccines, partly attributable to needle-phobia. It is predicted that this issue will persist unless a new strategy for vaccination is introduced. In this direct to Phase II proposal, we will explore the feasibility and potential benefits of a reduced dose intradermal strategy for HPV vaccines. In this larger study, we will evaluate doses and routes of administration to determine the immunogenicity, reactogenicity, and levels of patient and caregiver acceptance for each. In settings with minimal resources, the benefits of delivery with needle-free injection are predicted to include dose savings, increased compliance, and the prevention of needle-stick injuries and disease transmission. The results from these studies will provide clinical data to answer the main problems with the current HPV vaccine schedule: 1) availability of vaccine doses; 2) cost; and 3) acceptability & compliance. This data will be a first step to facilitate future policy discussions and global health strategies regarding administration of fiHPV vaccines across Indonesia and other developing countries. The immediate next steps will include planning a larger roll-out campaign across multiple areas of Indonesia, notably in further remote areas where vaccination compliance has been historically low. Ultimately, these studies will be used as a tool to increase awareness of the PharmaJet Tropis Needle- free injection system as a method for fiHPV administration that may aid in country-wide and worldwide vaccine compliance and acceptability to schedules as recommended by the WHO and Ministries of Health.

PROJECT NARRATIVE Cervical cancer is the fourth most common cancer in women, contributing to about 570,000 new cases and more than 300,000 deaths in 2018, mostly focused in low and middle-income countries (Bray, 2018). It has been shown that human papillomavirus (HPV) infection is the major causative agent of cervical cancer and while HPV vaccines have been introduced in approximately 100 countries globally, access and adherence to the vaccines in low- and middle-income countries is significantly lacking. This proposal seeks to carry out a clinical trial in Indonesia in order to collect data supporting the safety, efficacy, and acceptability of a fractional dose HPV vaccine administered with a commercial needle-free injection system. This information will be used to support global immunization programs in low- and middle-income countries and help prevent cervical cancer worldwide.