title: Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication.
abstract: OBJECTIVE
  Human papillomavirus (HPV) causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC) too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT) and Neo-adjuvant chemotherapy (NACT) patients with subsequent analysis of HPV profile.
  
  
  METHODS
  HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein) of the prevalent subtype was done.
  
  
  RESULTS
  High prevalence of HPV was observed in both PT (64.0%) and NACT (71.0%) cases with significant association with younger (20-45 yrs) PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21), fibro adenomas (30%, 3/10) to tumors (64.8%, 203/313) samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0%) followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839) in the LCR region and two (KT020836 and KT020837) in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314) and E6^E7*II (KU199315) fusion transcript variants.
  
  
  CONCLUSIONS
  Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients.
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Saimul
authors.initials: S
authors.lastname: Islam
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Hemantika
authors.initials: H
authors.lastname: Dasgupta
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Roychowdhury
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Rittwika
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Nupur
authors.initials: N
authors.lastname: Mukherjee
authors.affiliation: Department of Pathology, North Bengal Medical College and hospital, Sushruta Nagar, Darjeeling, West Bengal, India.
authors.forename: Anup
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of pathology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Gautam Kumar
authors.initials: GK
authors.lastname: Mandal
authors.affiliation: Department of Surgical Oncology, Chittaranjan National Cancer Institute37, Kolkata, West Bengal, India.
authors.forename: Neyaz
authors.initials: N
authors.lastname: Alam
authors.affiliation: Department of Surgical Oncology, Chittaranjan National Cancer Institute37, Kolkata, West Bengal, India.
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.affiliation: Department of Epidemiology & Biostatistics, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Shyamsundar
authors.initials: S
authors.lastname: Mandal
authors.affiliation: Saroj Gupta Cancer Centre and Research Institute, Thakurpukur, Kolkata, India.
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Chinmay Kumar
authors.identifier: http://orcid.org/0000-0002-0854-6978
authors.initials: CK
authors.lastname: Panda
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000821:virology*; D019295:Computational Biology; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000378:metabolism / Q000401:mortality / Q000821:virology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins