HPV-induced oropharyngeal cancer, immune response and response to therapy

Vu, Ha Linh; Sikora, Andrew G.; Fu, Shihua; Kao, Johnny

doi:10.1016/j.canlet.2009.06.026

Cited by 66 publications

(63 citation statements)

References 75 publications

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“…Indeed, infection by high-risk types of the human papilloma virus (HPV), most frequently type HPV16, has been found to be etiologically associated with an increasing number of patients with OPSCC (7)(8)(9). Although the majority of patients with HPVpositive OPSCC presents with an advanced stage of the disease at the time of diagnosis, these patients show a favorable prognosis independent of the therapeutic treatment regimen (10,11). HPVpositive OPSCCs show differences in viral load and viral oncogene expression that are closely associated with clinical outcome (8,10,12,13).…”

Section: Introductionmentioning

confidence: 99%

HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas

Kostareli¹,

Holzinger²,

Bogatyrova³

et al. 2013

J. Clin. Invest.

111

130

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High-risk types of human papilloma virus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). Strikingly, patients with HPV-positive OPSCC are highly curable with ionizing radiation and have better survival compared with HPV-negative patients, but the underlying molecular mechanisms remain poorly understood. We applied an array-based approach to monitor global changes in CpG island hypermethylation between HPV-negative and HPV-positive OPSCCs and identified a specific pattern of differentially methylated regions that critically depends on the presence of viral transcripts. HPV-related alterations were confirmed for the majority of candidate gene promoters by mass spectrometric, quantitative methylation analysis. There was a significant inverse correlation between promoter hypermethylation of ALDH1A2, OSR2, GATA4, GRIA4, and IRX4 and transcript levels. Interestingly, Kaplan-Meier analysis revealed that a combined promoter methylation pattern of low methylation levels in ALDH1A2 and OSR2 promoters and high methylation levels in GATA4, GRIA4, and IRX4 promoters was significantly correlated with improved survival in 3 independent patient cohorts. ALDH1A2 protein levels, determined by immunohistochemistry on tissue microarrays, confirmed the association with clinical outcome. In summary, our study highlights specific alterations in global gene promoter methylation in HPV-driven OPSCCs and identifies a signature that predicts the clinical outcome in OPSCCs.

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Section: Introductionmentioning

confidence: 99%

HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas

Kostareli¹,

Holzinger²,

Bogatyrova³

et al. 2013

J. Clin. Invest.

111

130

View full text Add to dashboard Cite

show abstract

“…Since the majority of deaths occurring in the first 5 years following diagnosis are attributed to primary cancer, further improvements in therapy would yield meaningful improvements in overall survival (19). The improved prognosis associated with oropharyngeal cancers in recent years may be related to increased utilization of concurrent chemoradiation, technological advances in radiation delivery and the increasing prevalence of HPV-related tumors (5,9,12). Caucasian ethnicity and high grade tumors have both been associated with HPV-related tumors and likely account for some of the improved prognosis observed in those subgroups (13,20).…”

Section: Discussionmentioning

confidence: 99%

“…Due to competing risks of second primary cancer and comorbid medical conditions related to smoking and alcohol use, overall survival remains consistently lower than disease-free survival (11). Recently, high-risk human papilloma virus (HPV) infection has emerged as an important risk factor for oropharyngeal carcinoma (12). HPV infection is now found in more than 50% of patients with oropharyngeal cancer and tends to affect younger patients irrespective of tobacco or alcohol use (13).…”

Section: Introductionmentioning

confidence: 99%

Competing causes of death in patients with oropharyngeal cancer treated with radiotherapy

Kao

Lau

Tong

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Radiation with or without chemotherapy is considered the mainstay of treatment for the majority of patients with oropharyngeal cancer. The goal of this study was to analyze competing causes of mortality in patients with oropharyngeal cancer with long-term follow-up. We queried the Surveillance, Epidemiology and End Results (SEER) database and identified 3728 patients with oropharyngeal cancer treated between 1988 and 2001 with definitive radiotherapy. We analyzed predictors of overall survival and risks of mortality from index oropharyngeal cancer, second primary cancer, cardiovascular disease and other causes using a cumulative incidence analysis and Cox multivariate analysis. With a median follow-up of 6.8 years, the 5-and 10-year overall survival was 37 and 22%, respectively. At 5 years, the risk of mortality from primary oropharyngeal cancer was 35%. Between years 3 and 10, 69% of mortalities were attributed to causes other than the index cancer. Despite advances in the non-surgical treatment of oropharyngeal cancer, patients remain at significant risk of cancer-and non-cancer-related mortality.

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“…This approach may be less toxic and thus better tolerated than one with concurrent chemoradiation; however, to our knowledge there has not been a clinical trial to address this issue. Second, recent evidence indicates that human papillomavirus (HPV)-associated head and neck cancers respond more favorably to multiple treatment modalities, including surgery, radiation, and concurrent chemoradiation (23,24). Hence, it is reasonable to expect this subset of patients to respond more favorably to our treatment regimen as well.…”

Section: Discussionmentioning

confidence: 99%

Toxicity profile and clinical outcomes in locally advanced head and neck cancer patients treated with induction chemotherapy prior to concurrent chemoradiation

Genden

Misiukiewicz

et al. 2011

Oncol Rep

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Abstract. The use of induction chemotherapy prior to chemoradiation for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) remains controversial. We explored whether toxicity from induction chemotherapy influenced the delivery of concurrent chemoradiation. Among 171 consecutive previously unirradiated patients with HNSCC treated with combined chemotherapy and radiation, we identified 66 patients with stage III-IVB head and neck carcinoma who were treated with induction chemotherapy prior to planned chemoradiation. The most common induction regimen was docetaxel, cisplatin and 5-FU (TPF; 80%) for 2 to 3 cycles. Mean radiation dose was 72 Gy (range, 36-75 Gy). Concurrent chemotherapy regimens included cisplatin (26%), cetuximab (5%) and 5-fluorouracil/hydroxyurea (65%)-based regimens. At a median follow-up of 27 months (range, 9-56 months), the 2-year locoregional control and distant control rates were 85 and 86%, respectively. The 2-year disease-free survival and overall survival rates were 74 and 80%, respectively. Although there were no grade 5 toxicities during induction chemotherapy, 26% of patients required hospitalization for adverse events, including 5% needing intensive care. The most common high grade adverse events were grade 4 neutropenia (21%) and neutropenic fever (17%). Six percent of patients were unable to tolerate concurrent chemotherapy. The 2-year disease-free survival was significantly higher in patients able to complete induction and concurrent chemoradiation as planned (83 vs. 27%, p<0.001). Induction chemotherapy followed by concurrent chemoradiation results in promising survival rates in our cohort of advanced head and neck carcinoma patients. Due to severe toxicities in a subset of patients, this strategy is only recommended in selected high-risk patients who are carefully followed by an experienced multidisciplinary team.

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HPV-induced oropharyngeal cancer, immune response and response to therapy

Cited by 66 publications

References 75 publications

HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas

HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas

Competing causes of death in patients with oropharyngeal cancer treated with radiotherapy

Toxicity profile and clinical outcomes in locally advanced head and neck cancer patients treated with induction chemotherapy prior to concurrent chemoradiation

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