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Global Translational Medicine The research advances in HPV integration

References [105] [15] [106] [107] [108] tumors since 2020, with a predominant focus on cervical
cancer in most publications. Emerging studies employing
multi-omics techniques (such as genomics, proteomics,
transcriptomics, and epigenomics) hold promise for
Genes into which HPV integrates at high frequency KIAA0825 SOX2, TP63, FGFR, MYC, CD274 MYC KLF5, LRP1B, KLF12, CADM2, CEP19, CSMD1, NRROS, and more (in total 24 genes with≥3 events) N/A (associated with CNVs) unveil new associations between biological entities and
offering multidimensional, integrative approaches to
relevant biomarkers.

5. Clinical significance
In the latest WHO guidelines for the screening and
treatment of cervical precancer lesions aimed at
preventing CC, HPV DNA testing is recommended

. However, genotyping alone proves
and treatment
Number of integration sites identified 1 (in oropharyngeal cancer) 874 N/A (focus on resolving the structures of genomic rearrangements flanking integration sites) 2,252 33 as the principal screening approach for diagnosis
[78]
effective solely in CC prevention. A more clinically
relevant strategy involves a combination of genotyping,
evaluation of integration status and sites, analyses of
epigenetic changes, and examination of tumor-related
. It is important
immune molecules (such as HLA-G)
[79]
9, covering HPV types 6, 11, 16, 18, 31, 33, 45, 52,
Infected HPV types 16 16, 18, 33, 35, 59, 69 16, 18 6, 16, 18, 33, 44, 51, 56, 58, 62, 66, 68 6, 16, 18 to note that nonvalent HPV vaccines, such as Gardasil
and 58, hold the potential to prevent up to 90% of all
cases of cervical cancer. While preventive vaccination
against HPV, especially HPV16 and HPV18, proves

there is a pressing need to expand vaccination efforts
Number of samples 2 oropharyngeal cancer tissues and 1 gastric cancer tissue 105 4-cell lines and 105 clinical samples 108 72 Abbreviations: ChIP-seq: Chromatin immunoprecipitation sequencing; ecDNA: Circular extrachromosomal DNA; FISH: Fluorescence in situ hybridization; HIVID: High-throughput viral effective in halting the spread of HPV-related cancers,
in developing countries. Moreover, the development of
new treatments, such as therapeutic vaccines, remains
imperative for addressing the unvaccinated aging
population suspected of HPV infection. Analyzing the
integration detection; HPV: Human papillomavirus; PCR: Polymerase chain reaction.
3’ rapid amplification of cDNA ends for the detection of E6/E7 fusion Long-read sequencing (PacBio HiFi and nanopore sequencing) and clinical and molecular associations, along with altered
landscape of HPV integration patterns has unveiled
signaling pathways that could serve as predictive,
prognostic, or therapeutic biomarkers for HPV-
.
associated mucosal neoplasia
[80]
Method (s) used Whole-genome sequencing whole-genome sequencing HIVID Whole-exome sequencing 5.1. Cancer risk assessment and predictive markers
Many studies have consistently demonstrated that HPV
RNA
integration is a prevalent event in the initial stages of
cervical carcinogenesis (such as CIN1). As the disease
progresses from CIN to cancer, both the rate and number

Technology Sanger sequencing Second-generation sequencing Third-generation sequencing Second-generation sequencing Second-generation sequencing of integration events increase. This underscores the
potential value of these markers as predictors of cancer
. The molecular profile of entire genomes
progression
[17]
displaying HPV integration can serve as an indicator of
the duration of CIN. Notably, utilizing a methylation
Table 1. (Continued) Cancer type Oropharyngeal cancer and gastric cancer Oropharyngeal cancer Penile squamous cell carcinoma Anal squamous cell carcinoma marker panel has proven to be a highly sensitive method
for screening CIN undergoing transformation. In a study
conducted by Liu et al.
, it was observed that methylated
[81]
CpG sites frequently co-occurred with integration sites
in the HPV16 genome. Clinical samples validated that a

Volume 2 Issue 4 (2023) 10 panel of CpG sites (nt5606, nt5609, nt5615, and nt5378)
https://doi.org/10.36922/gtm.2034