Cervical cancer is the second most malignancies in women in the world (Bruni et al., 2017). Concerning the epidemiology, it is estimated there are 528,000 new cases and 266,000 deaths in 2012 (Farley et al., 2015). If the number of cases continues to increase, it is estimated that by 2025 cervical cancer in the world will reach 20 million new cases. The main risk factor for cervical cancer is related to Human papillomavirus (HPV) infection in the cervical epithelium (Akyar et al., 2013; Manga et al., 2015; Nurcahyanti, 2016).
It is estimated that 5% of cancers in humans are caused by Human papillomavirus (HPV) infections, some of these cancers originate from cervical cancer. Type 16 HPV is a major cause of cervical cancer, with percentage, respectively, 45.5% in worldwide and 60% in Indonesia (Bruni et al., 2017). It is reported that 70% of cervical cancer caused by the infection of oncogenic type of HPV (high risk), and it is associated with anogenital cancers in men and women, such as cancer of the penis, vulva, vagina, anal, and oropharyngeal cancer (Setiawati, 2014). Approximately there are 100 different subtypes of HPV with different variations in potency and oncogenic, and which specifically infecting anogenital area are HPV types 16, 18, 31, 33, 35, 39, 45, 52, 52, 56, 58, 66, and 69 ( Faridi et al., 2011)
In the study of cervical cancer samples, it is proved the presence of HPV deoxyribonucleid acid (HPV DNA) was found in 99.7% cases and was dominated by types 16, 18, 31 and 45, this shows the role of high-risk HPV in the development of cervical cancer (Lipinwati, 2014).
Human papillomavirus (HPV) is a double-stranded, non-envelope DNA viruses measuring around 7,200-8,000 base pairs. It enveloped in capsid protein which is composed of L1 protein (major capsules) and L2 protein (minor capsid). The viral genome is divided into 3 regions, namely non-coding regions (initial regulation) or also known as long-control regions (LCR) of 400–1.000 bp, the second region is an initial region consisting of an Early Protein Open Reading Frame (ORF) such as E1, E2, E4, E5, E6 and E7, the third region is the region of late protein that encodes L1 and L2 proteins which form a viral capsids or viral envelopes, in which L1 and L2 capsids play a role in the transmission of HPV viruses (Blitzer et al., 2014).
L1 and L2 proteins have assembly properties into virus-like particles (VLP) that are important in eliciting effective immune responses; this has been used as an ideal target for HPV vaccines. The discovery of nucleotide differences in HPV variants lead to changes in amino acids that can interfere the structure, specific viral functional or antigenic characteristics which are considered important to distinguish potential transmission and to define epitopes that are relevant to vaccine design (Pillai et al., 2009, Buck et al., 2013)
Structural diversity present on the surface of L1 protein between different papillomavirus species is believed to depict the evolution of virus’s mutations that are antigenic diversity (Faust and Dillner, 2013 Frazer, 2014; Choi and Park, 2016).
Several studies have proven there are variations in the HPV-16 L1 gene in several countries. These L1 gene variations can affect viral binding that affect the structure or adjustment of proteins and ultimately lead to changes in biological function including host immunological recognition and affect the effectiveness of existing vaccines. According to El aliani's study, out of 35 samples, there are 17 nucleotide changes occurred, namely silent mutation and 5 missense mutations, the five missense mutations are A / C (6694), G / A (6801), G / A (6819), ATG Insertion (6903), and GAT Deletions (6950). But none of the 5 missense mutations affected the L1 immunogenic region, while A / C substitution (6694) in loop H-1 showed the potential impact of mutations to the effectiveness of existing anti-HPV vaccines (El-Aliani, 2017)