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Human papillomavirus (HPV) is a small and non-enveloped deoxyribonucleic acid (DNA) virus that infected mucosal cells. This viral genome is composed of early and late genes. Late (L) encodes the L1 and L2 proteins. The structural protein L1 is located outside the virion. It contributes to the viral attachment mechanism; hence it becomes the target for multi-strain vaccine design. This review aims to discuss the potency of conserved L1 HPV region and the innovation of multi-strain vaccines for prevention strategies of HPV infection. Bioinformatics methods in vaccine design applied for identification of conserved sequences from databases, epitopes map, antigenicity test, prediction of similarity, and autoimmune level. The multi-strain vaccine innovation initiated in this review has more benefits compared to previous vaccines based on the level of vaccine coverage via conserved regions, potential of immune cell …