Despite regular cytology screening becoming an effective tool in cervical cancer prevention, cervical cancer continues to pose a considerable threat in the developing parts of the world [24,25
]. Although Korea is no longer a developing country, the incidence and mortality rate of cervical cancer in Korea suggests that cervical cancer is still a major health concern in the region [2,3
]. Two studies which included Korean adolescents aged 10-14 years have been conducted previously to evaluate the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine [26,27
]. The present study was conducted in Korean girls 15-25 years of age.
In the present study, all women initially seronegative for anti-HPV-16 and -18 antibodies seroconverted at one month post-dose 3, with high antibody titres achieved against both antigens. Initially seropositive women exhibited comparable GMTs one month post-dose 3 as in the initially seronegative women. The GMT levels in the current study were at least 180 fold higher for both antigens one month post-dose 3 than those observed after natural infection with HPV-16/18 [16
]. The level of protection conferred and the immunity induced following a natural infection are unknown. However, it is shown that not all women develop serum antibodies to HPV after a natural infection [28
], and because antibodies after a natural infection are relatively low and do not reliably protect against re-infection, women who may have already been exposed to the infection are still susceptible to re-infection. Vaccination with the HPV-16/18 AS04-adjuvanted cervical cancer vaccine helps in inducing sustained antibody responses. The high immunogenicity, the role of novel AS04-adjuvant in the induction of high immune response and its implications have been shown and elaborated in a previous study in Korean pre-teens and young adolescents aged 10-14 years [27
]. Immunological superiority of the AS04-adjuvanted formulation has been observed before when compared to the same antigens adjuvanted with aluminium alone [29,30
Although the current study did not evaluate the efficacy of the vaccine, in a large international phase III study across 14 countries in women from 15-25 years of age (same age range as this study) [13,16
], the HPV-16/18 AS04-adjuvanted vaccine has demonstrated to be highly efficacious against infections and CIN2+ lesions associated with HPV-16 and HPV-18, with additional cross-protection against persistent infections and cervical lesions with other oncogenic non-vaccine types (i.e., HPV-31, HPV-33, and HPV-45). Magnitude of immune response (GMTs) achieved in this study was similar to that observed in the above global trial, and comparable to other HPV trials in women in Asia, Europe and North America, which indicates no ethnic differences, and similar efficacy can be expected in Korean women 15-25 years of age.
Although the study was not powered for safety evaluation, safety data generated in this study are similar to those shown in other global studies [13-17
]. Incidence of local injection site symptoms and some general symptoms was observed to be higher in the HPV group than in the ALU group, with grade 3 local and general symptoms being rare in both groups. The majority of AEs were generally mild and resolved within a couple of days, and compliance with vaccinations was high with over 90% women completing the full vaccination schedule. This is in line with the clinical experience with AS04-adjuvanted formulations confirming the HPV-16/18 AS04-adjuvanted vaccine to have a clinically acceptable safety profile in Korean women.
A rapid change is being observed in the sexual behaviour and social activity in Korea, with sexual debut becoming earlier in Korean women. This change has led to an increased risk of HPV infection in Korean women, which in turn has increased the incidence of cervical cancer in this region, as confirmed by two surveys conducted in Busan, Korea [31,32
]. Cervical cancer screening using the Papanicolaou test has helped in a considerable reduction in cervical cancer burden in Korea since its introduction in the 1950s in the region by the Korean Government [2,25
]. Regular screening has shown to reduce the ICC incidence in a prospective cohort study in Korea [33
]. However, participation of women in such screening programmes is shown to be marked by socioeconomic inequality, largely dependent on the socioeconomic status of women [34
]. Hence, immunisation of adolescents and young women before sexual debut can help in providing early protection as depicted in a previous study of Korean population of 10-14 years of age [27
], to complement the cervical cancer screening programme. Additional measures of increased disease awareness amongst young women and about the risks and benefits of vaccination and age-based interventions policy programmes can further facilitate to control the cervical cancer burden in Korea [2,25
In conclusion, the HPV-16/18 AS04-adjuvanted cervical cancer vaccine was shown to be highly immunogenic and has a clinically acceptable safety profile in the Korean population of 15-25 year olds, as previously shown in a Korean population of 10-14 year old adolescents and girls in another study. With cervical cancer being a major health problem in Korean women, prophylactic HPV vaccination may be integrated into routine immunisation programmes, in line with recommendations by the WHO, to help combat the cervical cancer disease burden.