HPV16 DNA and integration in normal and malignant epithelium: implications for the etiology of laryngeal squamous cell carcinoma.
Molecular evidence suggests that human papillomavirus (HPV) has a role in the etiology of oropharyngeal squamous cell carcinoma. However, the role of HPV in laryngeal squamous cell carcinoma (LSCC) is unclear.



We conducted a case-control study using tumor tissue specimens from 300 LSCC patients and vocal cord polyp specimens from 300 cancer-free controls. HPV genotype, HPV16 viral load and viral integration status, and p16 expression were determined.



The prevalence of HPV (all types) was higher in cases than controls [21 (7.0%) versus 10 (3.3%), adjusted odds ratio (aOR) 2.37, 95% CI 1.08-5.21]. The prevalence of HPV16 was higher in cases than controls [20 (6.7%) versus 8 (2.7%), aOR 2.84, 95% CI 1.21-6.68]. The risk of LSCC associated with HPV16 DNA positivity was even higher in patients aged 55 years or younger (aOR 3.52, 95% CI 1.07-11.54), males (aOR 4.74, 95% CI 1.33-16.90), never-smokers (aOR 5.57, 95% CI 1.41-22.10), and never-drinkers (aOR 3.72, 95% CI 1.09-12.72). HPV DNA was partly or fully integrated in all 20 HPV16-positive cases but was episomal in all 8 HPV16-positive controls; however, the HPV16-positive cases and controls had similar viral loads (P = 0.28). P16 immunostaining was positive in 31 of the 300 cases (10.3%) and negative in all 300 controls.



These results suggest that prior infection with HPV16 may play a role in the etiology of some LSCC. This larger case-control study will offer for the first time the possibility to address in depth the understanding of a tissue-specific role of HPV in laryngeal carcinogenesis. Further studies with larger samples are needed to confirm these findings.
Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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Chen
Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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L
Gao
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA.
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Sturgis
Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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Z
Liang
Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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Y
Zhu
Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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Xia
Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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Zhu
Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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X
Chen
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA.
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G
Li
Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
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Z
Gao
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D004848:Epithelium / Q000473:pathology / Q000821:virology; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D016662:Virus Integration / Q000235:genetics
D004279:DNA, Viral
head and neck cancer; human papillomavirus; laryngeal cancer; physical status; risk; viral load