title: Human papillomavirus infection correlates with inflammatory Stat3 signaling activity and IL-17 expression in patients with breast cancer.
abstract: OBJECTIVE
  Microbiota has been suggested in promoting chronic inflammation in human tissues which, in turn, promotes tumor development. This study tests a hypothesis that high-risk human papillomavirus (HR-HPV) infection may correlate with proinflammatory Stat3 signaling activities and IL-17 levels in breast cancer (BC) patients.
  
  
  METHODS
  This study examined HPV infection by GenChip technology, constitutively active Stat3 (p-Stat3) and IL-17 levels by immunohistochemistry (IHC) using specific antibodies in 379 BC patients, together with 245 paired adjacent breast adenosis (ABA) tissues and 100 unrelated breast adenosis (BA) tissues.
  
  
  RESULTS
  We obtained four major findings: (1) HR-HPV16/18 infections existed in 10.5% (34/325) of BC issues, higher than control BA tissues (4%, 4/100, P = 0.047). (2) Using IHC methodology, BC tissues showed more overactive p-Stat3 (2+/3+, 38.5%, 146/379) than ABA tissues (27.3%, 67/245, P < 0.001); similarly, BC also had more tissues overexpressing IL-17 (2+/3+, 61.5%, 233/379) than ABA tissues (51.8%, 127/245, P < 0.001). (3) High levels (2+/3+) of both active p-Stat3 and IL-17 correlated with poor differentiation and lymph nodal metastasis in BC (both with P < 0.05), but not with patients' prognosis. (4) HR-HPV infections correlated with both active p-Stat3 (P = 0.018) and its downstream IL-17 levels (P = 0.021) in BC tissues.
  
  
  CONCLUSIONS
  There may be a possible tri-lateral relationship among HPV infection, constitutive Stat3 activity and IL-17 level, whose collaborations could orchestrate a proinflammatory microenvironment in breast tissues by which promote carcinogenesis and/or facilitate progression of breast cancer.
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Current Address: Zhengzhou Central HospitalZhengzhou 450007, Henan, China.
authors: Nan
authors: N
authors: Zhang
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Xinjiang Medical UniversityUrumqi 830054, Xinjiang, China.
authors: Zhi Ping
authors: ZP
authors: Ma
authors: Department of Histology and Embryology, Shihezi University School of Medicine Shihezi 832002, Xinjiang, China.
authors: Ju
authors: J
authors: Wang
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, Zhengzhou Central HospitalZhengzhou 450007, Henan, China.
authors: Hui Li
authors: HL
authors: Bai
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Shihezi University School of MedicineShihezi 832002, Xinjiang, China.
authors: Yi Xin
authors: YX
authors: Li
authors: Department of Mental Health Center, Hubei General Hospital, Wuhan University School of Medicine Wuhan 430060, Hubei, China.
authors: Qin
authors: Q
authors: Sun
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Shihezi University School of MedicineShihezi 832002, Xinjiang, China.
authors: Lan
authors: L
authors: Yang
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Shihezi University School of MedicineShihezi 832002, Xinjiang, China.
authors: Lin
authors: L
authors: Tao
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Shihezi University School of MedicineShihezi 832002, Xinjiang, China.
authors: Jin
authors: J
authors: Zhao
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Shihezi University School of MedicineShihezi 832002, Xinjiang, China.
authors: Yu Wen
authors: YW
authors: Cao
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Shihezi University School of MedicineShihezi 832002, Xinjiang, China.
authors: Feng
authors: F
authors: Li
authors: Department of Pathology and The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineShihezi 832002, Xinjiang, China; Department of Pathology, The First Affiliated University Hospital, Shihezi University School of MedicineShihezi 832002, Xinjiang, China.
authors: Wen Jie
authors: WJ
authors: Zhang
keywords: IL-17; Inflammation; breast cancer; high-risk HPV; p-Stat3; prognosis