Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands.
Adenoid cystic carcinoma (SACC) is a rare malignancy, but a frequent subtype in minor and major salivary glands. The molecular alterations or biomarkers that underlie its development and progression as well as therapy outcomes are poorly characterized. The main study goal was to investigate reliable biomarkers and patient-related factors that may have impact on recurrence and long-term survival of SACC. The prevalence of human papilloma virus (HPV) in SACC was determined by HPV-DNA genotyping and p16 immunostaining. Epithelial growth factor receptor (EGFR), p53 and Ki-67 expression were also evaluated. Twenty-eight (42%) of 67 patients were HPV-DNA positive. Kaplan-Meier analysis indicated that SACC patients with metastases (P=0.03) had a poor overall survival (OS) and a shorter recurrence-free survival (P<0.001). Positive resection margins significantly predicted shorter recurrence-free survival (P=0.01). In the multivariate analysis, non-metastatic disease (P=0.033) and p16 positivity (P=0.005) have shown their prediction value for OS while non-metastatic disease (P=0.002), HPV positivity (P=0.041) and negative resection margin predicted a better recurrence-free survival. The present study documents for the first time the positivity for HPV infection and overexpression of certain markers (p16, Ki-67, EGFR and p53) used in diagnostics in SACC as well as characterizes clinical entities. These factors might be exploited in the future as biomarkers for its prognostic value. Using the clinical and pathological basis for predicting different outcomes could significantly facilitate SACC stratification and potentially directing treatment.
Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Xu
X
Qian
Clinic for Gynecology, Charité-Universitätsmedizin Berlin, Campus Mitte and Benjamin Franklin, Berlin, Germany.
Andreas M
AM
Kaufmann
Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Chao
C
Chen
Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Georgios
G
Tzamalis
Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Veit M
VM
Hofmann
Charité Comprehensive Cancer Center, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Ulrich
U
Keilholz
Department of Pathology, Campus Benjamin Franklin, Charité, Universitätsmedizin, Berlin, Germany.
Michael
M
Hummel
Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Andreas E
AE
Albers
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D012468:Salivary Gland Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D012469:Salivary Glands / Q000473:pathology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors