Human Papillomavirus (HPV) Detection by Chromogenic In Situ Hybridization (CISH) and p16 Immunohistochemistry (IHC) in Breast Intraductal Papilloma and Breast Carcinoma

The presence of human papillomavirus (HPV) in breast benign and malignant lesions detected by chromogenic in situ hybridization and immunohistochemistry for p16 was studied, including 33 intraductal papilloma, 34 ductal carcinoma in situ, and 56 invasive breast carcinoma cases with benign control groups. HPV infection, especially high-risk subtype, may play a role in the pathogenesis of breast cancer but is not associated with intraductal papilloma. Immunohistochemistry for p16 is not a good surrogate marker for HPV infection in breast lesions. Purpose: This study explored human papillomavirus (HPV) amplification in breast benign and malignant lesions by chromogenic in situ hybridization (CISH) and the concordance of p16 expression by immunohistochemistry. Patients and Methods: The presence of HPV6/11 and HPV16/18 in 33 cases of intraductal papilloma, 34 cases of ductal carcinoma in situ (DCIS), and 56 cases of invasive breast carcinoma (IBC) was evaluated using matched-background breast parenchyma and breast reduction as control groups. Association with clinicopathologic factors including prognosis was assessed. Results: HPV 6/11 was observed in 0 cases (0%) of breast reduction, one case (3%) of intraductal papilloma, 11 cases (32.4%) of DCIS, and eight cases (14.3%) of IBC. HPV 16/18 was detected in three cases of (9.1%) breast reduction, six cases (18.8%) of intraductal papillomas, 14 cases (41.2%) of DCIS, and 25 cases (44.6%) of IBC. There was no difference in the HPV status between intraductal papilloma and breast reduction. HPV amplification in intraductal papilloma did not associate with developing atypia or carcinoma after long-term follow-up. However, HPV 6/11 and HPV 16/18 amplification was significantly higher in both DCIS and IBC when compared with breast reduction (P<.05). Compared with background breast parenchyma, HPV 16/18 amplification was significantly higher in both DCIS and IBC (P=.003 and P=.013, respectively). No correlation between p16 immunohistochemical staining and either of the HPV CISH testing was found (P>.05). Conclusion: HPV infection was detected in both breast lesions and background parenchyma. HPV infection may play a role in the pathogenesis of breast cancer but is not associated with intraductal papilloma. Immunohistochemical stain for p16 is not a good surrogate marker for HPV infection in breast lesions. (C) 2021 Elsevier Inc. All rights reserved.