De-intensified treatment in human papillomavirus-positive oropharyngeal cancer

Oosthuizen, J C; Doody, Jaime

doi:10.1016/s0140-6736(18)32930-1

Cited by 14 publications

(9 citation statements)

References 11 publications

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“…Concurrent chemoradiation with 3 cycles of high-dose cisplatin is currently the standard treatment for locoregionally advanced OPSCC [ 22 ]. However, due to short- and long-term toxicities, and due to the fact that HPV-associated OPSCC is more sensitive to chemotherapy and radiation than HPV-negative OPSCC, there has been much interest in treatment de-escalation [ 23 , 24 ]. Some current strategies under investigation include weekly cisplatin instead of high-dose cisplatin, lower radiation dose, or decreased adjuvant radiation and/or chemotherapy after surgery [ 25 – 27 ].…”

Section: Discussionmentioning

confidence: 99%

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

et al. 2020

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Background Transoral surgery (TOS), particularly transoral robotic surgery (TORS) has become the preferred modality in the United States for the treatment of early stage oropharyngeal cancer, largely due to assumptions of fewer toxicities and improved quality of life compared to primary radiotherapy (RT). However, these assumptions are based on retrospective analysis, a subset of which utilize primary RT groups not limited to T1-2 stage tumors for which transoral robotic surgery is FDA approved. Thus, there is potential for underestimating survival and overestimating toxicity, including treatment related mortality, in primary RT. Methods Consecutive cases of early T-stage (T1–T2) oropharyngeal cancer presenting to the London Health Sciences Centre between 2014 and 2018 treated with RT or chemoradiation (CRT) were reviewed. Patient demographics, treatment details, survival outcomes and toxicity were collected. Toxicities were retrospectively graded using the Common Terminology Criteria for Adverse Events criteria. Results A total of 198 patients were identified, of which 82% were male and 73% were HPV-positive. Sixty-eight percent of patients experienced a grade 2 toxicity, 48% a grade 3 and 4% a grade 4. The most frequent toxicities were dysphagia, neutropenia and ototoxicity. The rates of gastrostomy tube dependence at 1 and 2 years were 2.5% and 1% respectively. There were no grade 5 (fatal) toxicities. HPV-positive patients experienced improved 5-year overall survival (86% vs 64%, p = 0.0026). Conclusions Primary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a reference for comparison for patients treated with primary transoral surgery.

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Section: Discussionmentioning

confidence: 99%

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

et al. 2020

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“…Given the high rate of survival and severe adverse effects from standard treatment protocols that significantly reduce quality of life for survivors, interest has grown in treatment de-escalation for HPV(+) oropharyngeal cancer patients. Unfortunately, two clinical trials that de-escalated treatment for all HPV(+) oropharynx cases or all with minimal smoking history resulted in worse survival [ 13 ], with both trials testing the substitution of cisplatin with cetuximab. These results suggest the need to identify the subset of patients who are most likely to benefit from de-escalation.…”

Section: Phenotypic Clinical and Molecular Characteristics Of Hpv-positive Hnscc And Evidence That They Are Not A Homogenous Groupmentioning

confidence: 99%

Molecular Tumor Subtypes of HPV-Positive Head and Neck Cancers: Biological Characteristics and Implications for Clinical Outcomes

Qin

Henry

et al. 2021

Cancers

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Until recently, research on the molecular signatures of Human papillomavirus (HPV)-associated head and neck cancers mainly focused on their differences with respect to HPV-negative head and neck squamous cell carcinomas (HNSCCs). However, given the continuing high incidence level of HPV-related HNSCC, the time is ripe to characterize the heterogeneity that exists within these cancers. Here, we review research thus far on HPV-positive HNSCC molecular subtypes, and their relationship with clinical characteristics and HPV integration into the host genome. Different omics data including host transcriptomics and epigenomics, as well as HPV characteristics, can provide complementary viewpoints. Keratinization, mesenchymal differentiation, immune signatures, stromal cells and oxidoreductive processes all play important roles.

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“…However, an additional ramification from this work is that male Appalachian or other populations with multi-factorial oropharyngeal tobacco exposure may actually be under-staged using current AJCC-8 guidelines. This is an important consideration, since National Comprehensive Cancer Network (NCCN) guidelines recommend staging and treatment dependent on p16 status 52 , 54 , where treatment de-escalation of HPV-associated oropharyngeal cancers continues to be evaluated 55 – 57 . Future efforts towards definitively determining the extent of HPV involvement in Appalachian OC/P and oropharynx through comprehensive p16 staining and PCR 58 will be required to better clarify the predominant factors underlying oropharynx-driven, stage-based disparities in past and future Appalachian cohorts.…”

Section: Discussionmentioning

confidence: 99%

Disparate survival of late-stage male oropharyngeal cancer in Appalachia

Papenberg

Allen

Markwell

et al. 2020

Sci Rep

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the United States Appalachian region harbors a higher cancer burden than the rest of the nation, with disparate incidence of head and neck squamous cell carcinomas (HnScc), including oral cavity and pharynx (oc/p) cancers. Whether elevated HnScc incidence generates survival disparities within Appalachia is unknown. To address this, HNSCC survival data for 259,737 tumors from the North American Association for Central Cancer Registries 2007-2013 cohort were evaluated, with ageadjusted relative survival (RS) calculated based on staging, race, sex, and Appalachian residence. tobacco use, a primary HnScc risk factor, was evaluated through the Behavioral Risk factor Surveillance System from Appalachian states. Decreased oc/p RS was found in stage iV Appalachian white males within a subset of states. The survival disparity was confined to human papillomavirus (HPV)-associated oropharyngeal cancers, specifically the oropharynx subsite. This correlated with significantly higher smoking and male smokeless tobacco use in most Appalachian disparity states. Lower survival of Appalachian males with advanced-stage HpV-associated oropharyngeal cancers suggests pervasive tobacco consumption likely generates more aggressive tumors at HpV-associated oropharynx subsites than national averages. comprehensive tobacco and HpV status should therefore be evaluated prior to considering treatment de-intensification regimens for HPV-associated oropharyngeal cancers in populations with high tobacco consumption. HNSCC involves the epithelium of the oral cavity, pharynx and larynx. OC/P cancers are a major HNSCC subset, with nearly 11,000 deaths predicted in the US in 2020 1. Risk factors include tobacco and alcohol use, and highrisk human papillomavirus (HPV) infection 2,3. OC/P cancers are subdivided into HPV-associated oropharynx (HPV-associated) and non-HPV-associated oral cavity, hypopharynx, and nasopharynx (non-HPV-associated) cancers 4. These designations are supported by studies indicating that non-HPV-associated cancers are primarily tobacco/alcohol induced, whereas HPV-associated cancers are predominantly caused by HPV infection 5. Furthermore, HPV-negative or non-HPV-associated cancers consistently have poorer outcomes than HPV-positive or HPV-associated cancers, segregating these cancers as distinct diseases with differential clinical management 6,7. While national incidence of non-HPV-associated cancers is decreasing due to tobacco cessation, HPV-associated cancers are increasing due to rising infection rates 8. Regarding race, blacks with HNSCC present with more advanced disease, are older and have worse survival than whites, denoting a racial disparity 9-11. Increased screening for HPV coupled with subsite analysis indicates that blacks with HNSCC have less HPV-positive cancer than whites, explaining differences in survival 12,13. Consistent with this, HPV-associated cancers continue to increase in white males and in rural areas 4,14,15. The Appalachian region encompasses 205,000 square miles across 420 counties in 13 contiguo...

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De-intensified treatment in human papillomavirus-positive oropharyngeal cancer

Cited by 14 publications

References 11 publications

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

Molecular Tumor Subtypes of HPV-Positive Head and Neck Cancers: Biological Characteristics and Implications for Clinical Outcomes

Disparate survival of late-stage male oropharyngeal cancer in Appalachia

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