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Microbes & Immunity Phylogenetic analysis of HPV16 L1 in Asia

accounting for nearly seven out of ten cervical cancers
reported globally. Further analysis reveals that this ratio
5
remains consistently similar regionally. HPV infection
remains a significant public health concern, particularly
in Asia, where cervical cancer accounts for a substantial
proportion of female cancer-related mortality. According to
the WHO reports, over 60% of cervical cancer cases in Asia
are linked to HPV-16 and 18, with variations in prevalence
across different countries. In Southern and Western Asia,
HPV-16 and 18 infections contribute to more than 80% of
cervical cancer cases. In addition, HPV-related anogenital
5
and oropharyngeal cancers are increasingly reported
among men, with incidence rates varying from 17 to
43 cases per million depending on geographical location.
5
In the Asian region, the rate of cervical cancer due to HPV-
16 and 18 infections is 68% among infected women, and
in Southern and Western Asia, this rate exceeds 80%. In
5
Asia, HPV-related anogenital and oropharyngeal cancers Figure 1. Schematic representation of the human papillomavirus-16
affect both men and women, with incidence rates ranging double-stranded circular DNA genome with 7,908 bp long. Early genes,
which are E1, E2, E4, E5, E6, and E7, are represented in blue. Late genes,
from 17 to 43 cases per million. However, the prevalence L1 and L2, are represented in yellow. P97 and P670 are promoters, and
of HPV-driven cancers remains significantly higher in pAE and pAL are polyadenylation signals, respectively, for early and late
women due to the strong association between HPV and regions. LCR is the long control region. 7
cervical cancer, which accounts for the majority of HPV- the viral infection cycle, where they interact with heparan
related malignancies. 5
sulfate. 14,15 The residues contained within these loops hold
HPV is a double-stranded DNA virus belonging significant functional importance. 14
to the Papillomaviridae family, with a genome size of
approximately 8 kb. Structurally, HPV consists of 72 The L1 major capsid protein self-assembles into virus-
6
capsomeres in an icosahedral formation, lacks an envelope, like particles (VLPs), and Food Drug and Administration
and has a diameter of 55 nm. Figure 1 shows a schematic (FDA)-approved HPV vaccines, such as Cervarix®,
6
®
®
representation of the HPV-16 double-stranded circular Gardasil , and Gardasil 9, are developed based on
DNA genome which eight proteins: E1, E2, E4, E5, E6, E7, VLPs. 3,16-19 The currently available U.S. FDA-approved HPV
®
L1, and L2. The E1, E2, E4, E5, E6, and E7 proteins are vaccines, including Cervarix®, Gardasil®, and Gardasil 9,
categorized as “early” proteins essential for the viral life are widely used across Asia, though their approval status
cycle, including genome replication, cell cycle regulation, and distribution policies vary by country. While Japan,
and cell growth in specific HPV types. Notably, the E6 and China, and South Korea have fully approved all three
E7 proteins play critical roles in oncogenesis by disrupting vaccines, some countries, such as Pakistan, have limited
the normal functions of p53 and pRb, thereby interfering access due to regulatory delays and cost-related challenges.
with key cellular processes. The “late” proteins, L1 and In addition, national immunization programs in certain
7,8
L2, form the major and minor capsid proteins, respectively, regions prioritize specific vaccines based on availability
constructing the virus’s capsid structure. 9 and cost-effectiveness considerations. HPV vaccination is
The major capsid protein L1 is important for recommended primarily for adolescents aged 9 – 14 years
understanding the antigenicity, diversity, and classification as part of national immunization programs, with catch-up
of HPV. HPV types are classified based on nucleotide vaccinations available for individuals up to 26 years old
9
similarity in their L1 sequences. To name a novel HPV in some countries. However, vaccine accessibility varies;
type, its L1 sequence similarity with other virus types must for instance, Japan and South Korea offer free HPV
be less than 90%; for novel subtypes, it must be below vaccination under government-funded programs, whereas
98%. 10,11 Despite its rather conservative characteristic, in countries like Pakistan and India, vaccination is often
specific sequences in the L1 protein can vary in loops. available only through private healthcare providers,
These surface loops are named BC, CD, DE, EF, FG, and making affordability a significant barrier to widespread
HI loops based on the beta strands that they connect. 3,12,13 uptake. HPV vaccine coverage varies significantly across
Moreover, the lysine residues on FG and HI loops have Asia. Japan and South Korea report high coverage rates
been identified as regions involved in the initial stages of exceeding 70%, while coverage remains below 30% in

Volume 2 Issue 2 (2025) 54 doi: 10.36922/mi.8410