No Common Cold: Viruses Can Cause HPV-Related Cancers
Transcript of No Common Cold: Viruses Can Cause HPV-Related Cancers
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No Common Cold: Viruses Can Cause HPV-Related Cancers
11/2/2020
Jason Chan, MDUCSF Radiation OncologyAssistant Professor
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Disclosures
None
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Learning Objectives
Understand how head and neck cancers caused by HPV differ from those caused by smoking
Understand the key role of radiotherapy in the treatment of HPV-associated oropharyngeal cancers
Become familiar with UCSF’s leading efforts in reducing side effects and improving quality of life in the treatment of HPV-associated oropharyngeal cancers
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de Martel, The Lancet Global Health, 20204
Infections responsible for 13% of cancers
Most common are H. pylori, human papillomavirus (HPV), hepatitis B (HBV), and hepatitis C (HCV)
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Human Papillomavirus (HPV)
Group of non-enveloped DNA Viruses Infect human epithelial (surface) cells Some strains cause warts Some strains cause cancer
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HPV causes uncontrolled growth of surface cells
Virus makes proteins E6 and E7 Unregulated growth of epithelial cells
of the skin and mucous membranes
Basal cells
Squamous cells
Mature and divide
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Chaturvedi, J Clin Oncol 2010Van Dyne, CDC Weekly 20187
Rising incidence of HPV-associated oropharyngeal cancer
Most head and neck cancers with decreasing incidence
One notable exception –oropharynx
Has overtaken cervical cancer as the most common HPV‐related cancer in the United States
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Lei, NEJM 20208
June 2020: HPV vaccine approved for oropharyngeal cancers
• HPV vaccine was approved for cervical cancer in 2006
• Oropharyngeal cancer incidence likely to decrease like cervical cancer
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HPV-Associated Squamous Cell CarcinomasSame culprits: HPV-16 ~90%, HPV-18 ~5%
Oropharynx Anus Cervix
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HPV-Associated Squamous Cell CarcinomasSame culprits: HPV-16 ~90%, HPV-18 ~5%
Oropharynx Anus Cervix
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NCCN v2.202011
Oropharynx Cancer Treatment
Early Stage‐ RT alone‐ Surgery ± post-operative RT ± chemo
Locally advanced‐ RT + chemo‐ Surgery ± post-operative RT ± chemo
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Alsahafi, Cell Death & Disease 201912
Head and Neck SCC Treatment Evolution
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Vann, Portal Design in Radiation Therapy13
UCSF was an early-adopter of IMRT (since 1997)
Old techniques of radiation therapy
Intensity-modulated radiation therapy
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70 Gy with High-Dose CisplatinCurrent standard of care irrespective of HPV status
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Treatments render most patients disease-free
Pre-treatment 3 month follow-up
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HPV vs. Smoking Head and Neck Cancers
Cause HPV SmokingSite Oropharynx Any
Age Younger Older
Socioeconomic Status High Low
Risk Factors Sexual behavior Alcohol, tobacco
Survival > 80% at 3 years 50% at 3 years
Incidence Increasing Decreasing
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Mork, NEJM 200117
2001: HPV associated with oropharynx cancer
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D’Souza, NEJM 200718
2007: different risk factors than other HN cancers
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Ang, NEJM 201019
2010: HPV status linked to longer survival
low risk: 3-year OS 93%
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HPV Status Included in Latest Staging GuidelinesAll three AJCC7 Stage IVA
AJCC8 Stage I AJCC8 Stage II AJCC8 Stage III
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De-IntensificationMaintain high cure rates while reducing long-term toxicities
Surgery Radiation Systemic
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Nichols, Lancet Oncol 201922
Need to test hypothesis rigorouslyCannot substitute Cisplatin with Cetuximab
RTOG 10-165-year OS 85% 78%
De-ESCALaTE2-year OS 98% 89%
Worse overall survivalSimilar acute and late toxicities
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Nichols, Lancet Oncol 201923
Need to test hypothesis rigorouslyCannot assume transoral surgery is less morbid than radiotherapy
Primary RT (68% chemo) had statistically superior swallowing scores, less pain and trend toward less shoulder dysfunction at 1 year compared to primary surgery (caveat: 71% had post-op RT)
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Many promising ways to de-intensify RT
Reduce definitive RT dose UNC/UFL: 60 Gy + cisplatinHN002 (PI Dr. Sue Yom): 60 Gy ± cisplatinECOG 1308: chemoselection for 54 Gy vs. 70 GyUC Davis: chemoselection for 54 Gy vs. 60 Gy
Reduce post-op RT dose ECOG 3311: omission of RT, 50 vs. 60 Gy, 66 GyMayo: 30-36 Gy
Reduce RT target size Penn: omit RT to primary site
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NRG HN-002 (Closed)PI: Sue Yom
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Presentation Title26
NRG HN-005 (Open)PI: Sue Yom
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Takeaways
Standard of care chemoradiation for locally advanced HPV-associated oropharyngeal cancer is associated with life-long debilitating side effects
Patients with HPV-associated oropharyngeal cancers tend to be younger, healthier, with less smoking history
UCSF is a leader in developing future standards for oropharyngeal cancer treatments