**Introduction**
Cervical cancer is caused by persistent human papillomavirus (HPV) infection. Prophylactic HPV vaccine is highly effective at preventing vaccine-type HPV infection and cervical cancer. Originally given as a three-dose schedule, it was revised to a two-dose schedule in 2014. More recently, in 2022, an off-label one-dose schedule is recommended by the World Health Organization for girls aged 9-20 years. There are currently six approved HPV vaccines (three bivalent, two quadrivalent and a nonavalent), but not all are recommended for one dose. Neutralising antibodies are thought to be the mechanism of protection, but the amount of antibody needed to protect has not been identified, mostly because HPV vaccines are so effective and there has been little or no breakthrough cases. Antibodies have multiple functions that can be broadly classified as neutralising or non-neutralising (Fc-mediated). Neutralising antibodies directly bind to the pathogen and prevent them from attaching to host cell surface. Non-neutralising antibodies binds to the pathogen but utilises the Fc portion of the antibody to activate immune cells to facilitate pathogen clearance. The role of non-neutralising antibodies in HPV protection is the subject of ongoing research.
**Fiji HPV immunological study cohort**
Fiji is a middle-income country in the Pacific and has one of the highest cervical cancer incidences in the region (age-standardised rate: 29.8 per 100,000 women). Cervical cancer is the 2nd most common cancer in Fijian women. In 2008/9, the Fiji Ministry of Health received a donation of quadrivalent HPV vaccine and organised a vaccination campaign to vaccinate >30,000 girls aged 9-12 years old with a three-dose schedule. However, due to various reasons, some girls only received one or two doses. Fiji introduced the bivalent HPV vaccine into their national program in 2013. In 2015, we recruited girls who were either unvaccinated or previously vaccinated with one, two or three doses of quadrivalent HPV vaccine during the 2008/9 campaign to measure persistence of HPV immunity (6 years-post immunisation). All girls were given an additional dose of bivalent vaccine as catch-up vaccination. This provided an unique opportunity to measure HPV immunological memory responses.
**A Unique Cohort Driving the Single-Dose HPV Vaccine Recommendation**
The Fiji cohort was one of only four longitudinal cohorts globally at the time that contributed to the evidence of long-term protection after one dose of HPV vaccine. Other longitudinal cohorts include the Costa Rica study, India IARC study and the Mongolian study. The Fiji cohort is also the only cohort globally that was given a booster dose, allowing the investigation of immune memory responses following one dose of HPV vaccine.
This valuable cohort has generated crucial evidence supporting the one-dose HPV vaccine schedule, along with multiple publications advancing the understanding of immunity from a single dose. Notably, the latest paper published in Nature Communications describes antibody profiles and non-neutralizing antibody functions following one dose of HPV vaccine. This paper utilises a high-throughput multiplex bead array assay to measure the antibody profiles (i.e. IgG1-4, IgA1-A2, IgM) among the Fijian cohort and compare their antibody responses between those who were unvaccinated or who previously received one, two or three doses of quadrivalent vaccine.
Novel findings from the paper were that one dose of HPV vaccine generated similar antibody profiles and non-neutralising antibody function, specifically antibody-dependent cellular phagocytic function as two or three doses. This was observed at six years following vaccination, contributing to evidence of the persistence of one dose HPV immunity. Furthermore, antibody concentrations, particularly IgG1/IgG3, antibody profiles and phagocytic function were similar following a dose of bivalent HPV vaccine, between previously vaccinated girls, indicating robust immune memory after one dose. This is the first evidence of its kind to report durable immune memory following one dose of HPV vaccine.
**Opportunities and Challenges**
Along this successful journey, productive collaborations with investigators from various national and international institutions have played a crucial role, fostering opportunities for ongoing partnerships. This program has facilitated technology transfer to multiple countries in the region, including Thailand, Malaysia, Vietnam, and Indonesia, empowering local researchers to conduct HPV vaccine evaluations locally and ultimately contribute to reducing cervical cancer in the region.
Funding has been a major challenge, as it is across the global research community. For this research, it was a bittersweet achievement—we managed to carry out this research with very limited funding, but the constraints have significantly prolonged the process, delaying the release of these important new findings.
**What’s next**
Current evidence suggests protection for at least 10 years and follow up of existing longitudinal cohorts such as those in Fiji will be crucial in understanding the duration of protection and to gain insights into the basis of how one dose of HPV vaccine is so potent. This information will inform HPV vaccination schedules globally and guide future vaccine design.
Our next steps will be to conduct a follow-up study in Fiji to evaluate the effectiveness of one dose of the HPV vaccine after 17 years. This study will be done on a different cohort of participants who did not receive the bivalent HPV vaccine after 6 years. Blood samples will be collected from participants to evaluate HPV vaccine immunity. This will be one of the longest follow up studies of one dose HPV vaccination. The impact of this research will be substantial by directly informing global HPV vaccination.
The HPV vaccine is highly effective at preventing cervical cancer (and other anogenital and oral cancers) and should be accessible globally. Giving only one dose of HPV vaccine has improved accessibility more than ever before. At least 57 countries have implemented one dose HPV vaccine schedule. While more countries are beginning to introduce HPV vaccine into their immunization programs, increasing uptake remains a key challenge, particularly in the face of vaccine hesitancy and misinformation. There is a need for stronger education and advocacy efforts, including public health campaigns, community engagement, and evidence-based communication strategies to build trust and promote vaccine acceptance.