Four novel subgenotypes (C6, C11, C12, and D6) of hepatitis B virus (HBV) were identified in Papua, a multiethnic province of Indonesia. To characterize the HBV strains in Papua, serum samples collected from 515 indigenous inhabitants (mean age: 26.6 +/- 9.6 years) in a previously unexamined area, Nabire, located in northern Papua, were used in the present study. Among 46 samples whose 1.6-kilobase (kb) HBV DNA sequence was amplified, 38 (83%) were typeable into known subgenotypes [B3 (n = 4), Cl (n = 2), C5, (n = 1), C6 (n = 5), C12 (n = 13), and D6 (n = 13)]. An analysis of the full-length sequence of the eight remaining HBV/C isolates whose sequence was either unclassifiable or uncertain within the 1.6-kb sequence showed no significant evidence of recombination in six isolates, and inter-genotypic recombination in two isolates (NAB20 and NAB46). By pairwise comparisons and a maximum-likelihood phylogenetic analysis, six non-recombinant isolates were considered significantly remote from known HBV/C isolates of subgenotypes C1-C12, and were classifiable into four novel subgenotypes (tentatively designated C13-C16). NAB20 and NAB46 were hybrids of C13/B3 and C12/G, respectively, displaying recombination breakpoints in the 5'-terminus of the P gene. Notably, the distribution of presumably indigenous subgenotypes C11-C16 was associated with particular language speakers in Papua. (C) 2011 Elsevier B.V. All rights reserved.