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Int J Clin Exp Pathol 2013;6(10):2168-2177

Original Article
Detection of high-risk human papillomavirus subtypes in cervical glandular neoplasia by
in situ hybridization

Zhang Sheng, Hiroshi Minato, Toshiyuki Sasagawa, Satoko Nakada, Eriko Kinoshita, Nozomu Kurose, Takayuki Nojima, Satoru Makinoda
Department of Pathology and Laboratory Medicine, Department of Obstetrics and Gynecology, Kanazawa Medical University, Kahoku, Ishikawa,

Received August 5, 2013; Accepted August 20, 2013; Epub September 15, 2013; Published October 1, 2013

Abstract: In situ hybridization (ISH) was performed on paraffin-embedded tissues to detect multiple high-risk human papillomavirus (HPV)
subtypes in 27 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma (CA) specimens. These results were compared with those
of HPV detection by HPV-PCR genotyping and p16 immunohistochemistry in the same specimens. Of the 27 cases, 17 (63%) showed
HPV-DNA by HPV-ISH, including 3 metastatic lesions. HPV-DNA was detected in 18 cases (67%) by PCR. The concordance rate between
HPV-ISH and HPV-PCR genotyping was 74% with moderate agreement (Kappa value, 0.41). HPV-16 was identified in 5 cases, HPV-18 in 2
cases, and HPV-45 in 1 case. Combining the results of HPV-ISH and HPV-PCR/genotyping, 22 cases (81.5%) were considered HPV positive.
Immunohistochemical staining of p16 indicated that 25 (93%) cases were positive; however, 4 of these cases were HPV-negative by both PCR
and ISH. Combining HPV-ISH and HPV-PCR/genotyping techniques demonstrated a high sensitivity of HPV detection in FFPE tissues from
cervical glandular neoplasias. In contrast, p16 immunohistochemistry seemed to have a low specificity for determining HPV status in cervical
glandular neoplasia. HPV-ISH is useful for recognizing the distribution of HPV in AIS and CA tissues and visualizing signal patterns, and may
be a useful tool to confirm the cervical origin of neoplasias and metastatic lesions. (IJCEP1308011).

Keywords: Uterine cervical cancer, adenocarcinoma, human papillomavirus, in situ hybridization, PCR, p16INK4A

Address correspondence to: Dr. Hiroshi Minato, Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1
Daigaku, Uchinada, Kahoku, Ishikawa, Japan 9200293. Tel: 81-76-218-8017; Fax: 81-76-218-8440; E-mail: hminato@kanazawa-med.ac.jp