Transcriptional activity of HPV in inverted papilloma demonstrated by in situ hybridization for E6/E7 mRNA.
OBJECTIVE
Assess human papilloma virus (HPV) transcriptional activity in inverted Schneiderian papillomas (IPs).


METHODS
Case series with chart review.


METHODS
Academic tertiary care center.


METHODS
Retrospective clinicopathologic review of 19 cases of IP in patients undergoing surgical excision from 1995 to 2013 at Mayo Clinic in Rochester, Minnesota. Surgical pathology archival material was histopathologically reviewed using hematoxylin and eosin-stained slides. Formalin-fixed, paraffin-embedded material from each case was evaluated for p16 expression using immunohistochemistry as well as HPV DNA and E6/E7 messenger RNA (mRNA) transcription using polymerase chain reaction (PCR) and in situ hybridization (via RNAscope technology), respectively.


RESULTS
Eight patients were female (42%), with an average age of 53 years (range, 23-82 years). Three demonstrated malignancy, and 5 subsequently recurred. Average follow-up was 49 months (range, 0-200 months), and 1 patient died from squamous cell carcinoma arising from the IP. RNAscope detected HPV mRNA transcripts exclusively within IP in 100% of cases; however, in 11 patients (58%), less than 1% of cells exhibited transcriptional activity. Only 2 of 19 cases (11%) demonstrated mRNA activity in 50% or more cells. HPV DNA was detected in only 2 specimens by PCR.


CONCLUSIONS
This study reveals wide prevalence but limited transcriptional activity of HPV in IP. No correlation between HPV transcriptional activity and progression, recurrence, or malignant transformation was identified. These data suggest that transcription of HPV may contribute to the pathogenesis of IP, but prospective data are needed to definitively demonstrate this connection. These results also suggest that RNAscope may be more sensitive than PCR in detecting HPV activity in IP.
Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota, USA stoddard.david@mayo.edu.
David G
DG
Stoddard
Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Michael G
MG
Keeney
Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Ge
G
Gao
Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA.
David I
DI
Smith
Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Joaquín J
JJ
García
Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota, USA.
Erin K
EK
O'Brien
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000473:pathology / Q000821:virology; D009363:Neoplasm Proteins / Q000378:metabolism; D009669:Nose Neoplasms / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D018308:Papilloma, Inverted / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012189:Retrospective Studies; D015533:Transcriptional Activation; D055815:Young Adult
C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015344:DNA Probes, HPV; D004279:DNA, Viral; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger
RNAscope; Schneiderian papilloma; human papilloma virus; inverted papilloma; mRNA in situ hybridization