HPV oropharyngeal cancer

HPV has been implicated in the pathogenesis of head and neck squamous cell carcinoma. 

HPV causes 70-90% of oropharyngeal squamous cell carcinomas.

The incidence of HPV positive oropharyngeal cancer has been increasing in the US and worldwide.


The incidence of oral pharyngeal squamous cell carcinoma, has increased nearly 3% annually among men in the US since 2001 and continues to rise.

I mean age of HPV oropharyngeal disease is 55-75 years of age.

HPV positivity is seen in all areas of head and neck cancer.


HPV oral pharyngeal cancers make up about 17,950 new cases and attributed to 3640 deaths in 2020.


The risk of death has been shown to be 60-80% lower with conventional therapy compared with HPV-negative oropharyngeal cancers.


A subset of patients with HPV associated cancer with favorable prognosis cancers that overexpress p16 and lower levels of p53 and Rb expression.


p16 positivity is associated with a five-year local regional control rate of 58%, and overall survival of 62%.


Conventional treatments including surgery, radiation and chemo therapy have good efficacy in these patients, but in those who relapse with distant disease the outcomes are dismal.

Patients with oropharyngeal cancers that are both HPV positive p16 positive have a better five-year overall survival in five years disease-free survival than patients  with tumors that are HPV negative/P16 negative.

Reduced radiotherapy volume and a dose of 30 Gy to the elective regions with concurrent chemotherapy with locally advanced human papillomavirus positive oropharyngeal carcinoma is associated with a 24 month local regional control of 97% an overall survival of 95.1%.

Patients with HPV associated head and neck cancers are usually younger, healthier, have less lifestyle risk factors then patients who did not have HPV-driven malignancy.

over 85% of patients with HPV related oropharyngeal cancer can be cured when treated appropriately, including those with advanced disease.

Head and neck squamous cell cancer occurs in patients with HPV infections that are persistent.


Approximately one and nine men between the ages of 18-69 is infected with oral HPV.


HPV infection may lead to an overexpression a viral oncogenes E6  and E7. 


Viral oncogene E6 binds cycle cell regulatory proteins p53 leading to its degradation and subsequent uncontrolled tumor cell growth. 


E7 has an additive oncogenic function binding to and degrading Rb, a tumor suppressor that  blocks exit from the G1 phase of the cell cycle, thus regulating E2F transcription factors.


HPV infection is responsible for the largest number of oral pharyngeal tumors in the US, counting for 45-90% of cases.


HPV positivity is detected in 25% of all head and neck squamous cell cancers.


Survival is markedly higher in patients with HPV associated head and neck cancers compared with those with negative HPV head and neck cancers-three year survival rate of 84% compared with 57%, respectively.


HPV positive head and neck squamous cell cancers have more markers of immune infiltration in CD8positive T-cell activation than HP negative head and neck squamous cell  cancers, a target for harnessing adaptive anti-tumor immune response systems.


HPV positive malignancy is associated with cell cycle regulation escape with the development of T cell tolerance to HPV infection, reduced regulation by interferon gamma, unbalanced signal transducer and activator of transcription (STAT) 1 and 3 signaling, secretion of immunosuppressive cytokines, expression of programed cell death ligand-1 and down regulation of human leukocyte average expression and processing which allows the immune system to recognize and tag tumors before destruction.


HPV infection with high-risk types 16, 18, 31, and 33 plays a causal role in oral pharynx squamous cell carcinoma.


More than 90% of HPV associated oral pharyngeal squamous cell carcinoma is attributed to high risk type 16, with rare findings of type 18, 33, and others.


HPV positive tumors have higher levels of CD8 positive T cell activation and higher expression of performin and grandzyme A and B , indicating immune activity.


There is a higher expression of cytotoxic T lymphocytes associated antigen-4 in HPV positive head and neck cancers.

Circulating tumor HPV DNA is useful for surveillance of HPV positive oropharyngeal squamous cell carcinomas.

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