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HPV (Human Papilloma Virus)

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 22 October 2012, last major update October 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

See also Cervix-cytology chapter: HPV,   HPV testing,   SIL-general


● Nuclear antigen; detection methods include PCR, in-situ hybridization, immunohistochemistry
● Can also detect via E6/E7 protein, p16 or ProExc (see below)
● Note: must understand what HPV subtypes / components the particular detection method targets


● HPV E6 protein induces p53 degradation by a ubiquitin-dependent pathway; also activates host cell telomerase
● HPV E7 protein binds retinoblastoma protein, leading to release of E2F transcription factor, then cell cycle progression
● E7 also interferes with p21 inhibition of cdk2, causing stimulation of S phase genes cyclin A and E

Uses by pathologists

● At any site, detection of HPV in lesions without typical histologic findings or in equivocal cases (Am J Dermatopathol 2012 Oct 9 [Epub ahead of print])
● Triage specimens with ASCUS into high risk (HPV+) or low risk (HPV-)
● Differentiate endocervical adenocarcinoma (usually HPV+) from endometrial adenocarcinoma (usually HPV-, Am J Surg Pathol 2002;26:998, Am J Surg Pathol 2010;34:915)
● Distinguish lung metastases from oropharyngeal squamous cell carcinoma (HPV+) from lung primary squamous cell carcinoma (HPV-, Am J Surg Pathol 2012;36:142)
● Determine aggressiveness of basaloid squamous cell carcinomas of head and neck (aggressive: HPV-, less aggressive: HPV+, Am J Surg Pathol 2008;32:1044)
● Testing for HPV E6/E7 transcripts by RNA ISH confirms presence of integrated and transcriptionally active virus (Am J Surg Pathol 2012 Oct 10 [Epub ahead of print])
● p16 immunohistochemistry (Am J Surg Pathol 2012;36:945, Am J Clin Pathol 2010;134:12) and ProExC immunocytochemistry (Am J Surg Pathol 2008;32:899, Cancer Epidemiol Biomarkers Prev 2011;20:628) are also useful to detect HPV

Micro images

Anal squamous neoplasia: HPV L1 capsid - various images

Cervix: normal

Cervical condyloma

Cervix: low grade SIL

Cervix: high grade SIL

Cervix: squamous cell carcinoma

Cervix: large cell neuroendocrine carcinoma (ISH)

Eye: conjunctival tumors are HPV+ by ISH

Eye: conjunctiva and lacrimal sac squamous tumors are HPV+ by PCR and ISH (figures 3-6)

Oropharyngeal squamous cell carcinoma: HPV ISH and p16

Oropharyngeal squamous cell carcinoma: staining of Langerhans cells

Positive staining - normal

● None

Positive staining - disease

● HPV related lesions (condyloma, squamous papilloma; many dysplastic, in situ or invasive carcinomas of anus, cervix, penis and vulva; also other sites)
● Bowen's disease of skin
● HPV L1 nuclear capsid: 38% of anal squamous cell carcinoma in situ, usually L1 negative in associated invasive carcinomas, Am J Clin Pathol 2011;135:436)
● Langerhans cells in oropharyngeal squamous cell carcinoma (J Appl Oral Sci 2011;19:378)

Negative staining

● Normal cervix (may have nonspecific background staining)
● Endocervical glandular atypia / dysplasia (usually)
● Sebaceous carcinoma
● Verruciform xanthoma
● Verrucous carcinoma

End of Stains > HPV (Human Papilloma Virus)

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