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Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma Survival: A Comparison by Tumor Site and Initial Treatment

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Abstract

Recent evidence suggests that human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) patients have better survival than HPV-negative patients. However, it is unclear if similar patterns for survival exist across different tumor sites, and whether HPV-associated prognosis is modified by type of treatment. We prospectively tested 222 histologically confirmed HNSCC primary tumors for HPV DNA by PCR and HPV E6/E7 RNA by RT-PCR prior to treatment at a large urban health center. Cox proportional hazard ratio models were constructed to assess HPV-associated differences in overall and disease-specific survival adjusting for clinical and demographic covariates. HPV detection varied significantly by primary HNSCC tumor site, from 35 % for oropharynx, to 25 % for hypopharynx, 5 % for larynx, and 3 % for oral cavity (p < 0.0001), with HPV16 accounting for the majority (95 %) of HPV-positive tumors. The hazard-risk of overall and disease-specific death comparing HPV16-positive versus negative oropharyngeal HNSCC was reduced by 74 and 89 %, respectively (p values < 0.05), and was independent of other prognostic indicators; no statistically significant changes in outcomes were observed for non-oropharyngeal HNSCC sites. Prediction of overall survival was better with combined DNA and RNA HPV16 positive PCR detection. There was no difference in HPV16-associated survival whether patients received either surgery or (chemo)radiotherapy as their initial treatment modality. Improved HPV-associated HNSCC survival is limited to patients with oropharyngeal primaries. No selective treatment advantage is observed for HPV-positive tumors, although clinical trials are needed to evaluate which treatment modalities provide the most benefit for HPV-positive HNSCC.

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Acknowledgments

We thank the participants of this study; Margaret Brandwein-Gensler for her help with pathological staging and processing of tissue specimens; Catherine Sarta for her time and effort spent enrolling participants and with data entry; Gregory Rosenblatt for his assistance with data management; and Leslie Adrien for her help preparing and handling the biospecimens for molecular analysis. This work is supported in part by the National Cancer Institute [grant number CA115243]; National Institute of Dental and Craniofacial Research [T32 training grant DE007255]; the Einstein Cancer Research Center (P30 grant CA013330); and the Departments of Otorhinolaryngology-Head and Neck Surgery and Pathology at Albert Einstein College of Medicine and Montefiore Medical Center.

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Authors and Affiliations

  1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10641, USA

    Christian R. Salazar, Robert D. Burk & Nicolas F. Schlecht

  2. Department of Pathology, Albert Einstein College of Medicine, New York, NY, USA

    Richard V. Smith, Nicole Kawachi, Nicole Anayannis, Thomas J. Belbin & Michael B. Prystowsky

  3. Department of Otorhinolaryngology, Head and Neck Surgery, Albert Einstein College of Medicine, New York, NY, USA

    Richard V. Smith, Madhur K. Garg, Missak Haigentz Jr. & Bradley A. Schiff

  4. Department of Radiation Oncology, Albert Einstein College of Medicine, New York, NY, USA

    Madhur K. Garg

  5. Division of Oncology, Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA

    Missak Haigentz Jr. & Nicolas F. Schlecht

  6. Division of Genetics, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA

    Robert D. Burk

  7. Department of Pathology, Montefiore Medical Center, New York, NY, USA

    Michael B. Prystowsky

  8. Department of Otorhinolaryngology, Head and Neck Surgery, Montefiore Medical Center, New York, NY, USA

    Richard V. Smith & Bradley A. Schiff

  9. Department of Radiation Oncology, Montefiore Medical Center, New York, NY, USA

    Madhur K. Garg

  10. Department of Oncology, Montefiore Medical Center, New York, NY, USA

    Missak Haigentz Jr.

  11. Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, USA

    Robert D. Burk

  12. Department Obstetrics, Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY, USA

    Robert D. Burk

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  1. Christian R. Salazar
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  2. Richard V. Smith
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  3. Madhur K. Garg
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Correspondence to Nicolas F. Schlecht.

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Salazar, C.R., Smith, R.V., Garg, M.K. et al. Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma Survival: A Comparison by Tumor Site and Initial Treatment. Head and Neck Pathol 8, 77–87 (2014). https://doi.org/10.1007/s12105-013-0486-4

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