HPV Associated Head and Neck Cancer
Abstract
:1. Introduction
2. HPV and HNC
3. Clinical and Demographic Features of HPV+ HNC
4. Molecular Alterations in HPV+ vs. HPV− HNC
5. Determination of HPV Status and HPV as a Biomarker
5.1. MicroRNAs as Biomarkers for HPV+ HNC
5.2. Circulating Biomarkers for HPV+ HNC
6. Therapeutic Perspectives: Treatment of HPV+ HNC as a Distinct Entity
HPV Subtype Specific Treatment Considerations
7. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
AJCC/UICC | American Joint Committee on Cancer/Union for International Cancer Control |
CLC | circulating lymphocyte count |
CMC | circulating monocyte count |
CNC | circulating neutrophil count |
CTC | circulating tumour cell |
DFS | disease free survival |
DM | distant metastases |
FFPE | formalin-fixed paraffin-embedded |
HNC | head and neck cancer |
HNSCC | head and neck squamous cell carcinoma |
HPV | human papillomavirus |
HPV+ | human papillomavirus positive |
HPV− | human papillomavirus negative |
IHC | immunohistochemistry |
IMRT | intensity-modulated radiation therapy |
ISH | in situ hybridization |
LN | lymph node |
miRNA | microRNA |
NCIN | National Cancer Institute |
OPC | oropharyngeal carcinoma |
OS | overall survival |
OSCC | oral squamous cell carcinoma |
PCR | polymerase chain reaction |
pCR | pathologic complete response |
PFS | progression free survival |
PY | pack years |
pRb | retinoblastoma protein |
qRT-PCR | quantitative real-time polymerase chain reaction |
RPA | recursive partitioning analysis |
TCGA | The Cancer Genome Atlas |
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Method | Principle | Advantage | Disadvantage | Ref |
---|---|---|---|---|
HPV16 E1 PCR | HPV16, the most common HPV subtype implicated in HNC, is quantified by qRT-PCR in DNA extracted from bulk tumour tissue | Highly sensitive | False positives may occur; technically more difficult to perform than IHC/ISH; detects only HPV16 | [10] |
p16 IHC | p16 is upregulated indirectly via repression of pRb by E7; loss of p16 is common in HPV- HNC | Technically easy to perform and clinically feasible; comparatively low cost | Indirect method of HPV detection; does not distinguish between HPV subtypes | [10] |
HPV16 ISH | HPV16, the most common HPV subtype implicated in HNC, is quantified and directly visualized in tumour cells | Technically easier to perform and clinically feasible; comparatively low cost; allows direct visualization of HPV in tumour nuclei | Detects only HPV16 | [10] |
RNA-Seq | Specific HPV viral transcripts can be detected by sequencing RNA transcripts | Accurate method for detecting HPV positivity and HPV subtype | High cost; technically difficult, requiring specialized resources; limited clinical feasibility at present | [14] |
DNA Sequencing | HPV can be detected by DNA sequencing | Accurate method for detecting HPV positivity and HPV subtype | High cost; technically difficult, requiring specialized resources; limited clinical feasibility at present | [48] |
Roche Linear Array | Detection of HPV by PCR amplification of DNA using HPV subtype specific primers | Accurate method for detecting HPV positivity and HPV subtype; most accurate method for resolving the presence of multiple HPV subtypes in one sample | Requires specialized resources; limited clinical feasibility at present | [48] |
MicroRNAs | HNC Subtype | Expression in HNC ¥ | Role as Biomarkers | Ref |
---|---|---|---|---|
miR-20b, miR-9, miR-9* | OPC | miR-9, miR-9* (up) | Associated with HPV/p16-status | [53] |
miR-20b (down) | ||||
miR-107, miR-151, miR-492 | OPC | miR-107, miR-151(up) | Correlated with overall survival | [53] |
miR-492 (down) | ||||
miR-20b, miR-107, miR-151, miR-182, miR-361 | OPC | miR-107, miR-151, miR-182, miR-361 (up) | Correlated with disease free survival | [53] |
miR-20b (down) | ||||
miR-151, miR-152, miR-324-5p, miR-361, miR-492 | OPC | miR-151, miR-324-5p, miR-361 (up) | Correlated with distant metastases | [53] |
miR-152, miR-492 (down) | ||||
let-7d, miR-205 | HNSCC | down | Associated with disease free and overall survival | [54] |
miR-210 | HNC overall | down | Associated with hypoxia; correlate with reduced overall and disease free survival | [55] |
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Spence, T.; Bruce, J.; Yip, K.W.; Liu, F.-F. HPV Associated Head and Neck Cancer. Cancers 2016, 8, 75. https://doi.org/10.3390/cancers8080075
Spence T, Bruce J, Yip KW, Liu F-F. HPV Associated Head and Neck Cancer. Cancers. 2016; 8(8):75. https://doi.org/10.3390/cancers8080075
Chicago/Turabian StyleSpence, Tara, Jeff Bruce, Kenneth W. Yip, and Fei-Fei Liu. 2016. "HPV Associated Head and Neck Cancer" Cancers 8, no. 8: 75. https://doi.org/10.3390/cancers8080075