Stains & molecular markers
HPV (Human papillomavirus)

Topic Completed: 1 October 2012

Minor changes: 4 November 2020

Copyright: 2002-2021,, Inc.

PubMed Search: HPV [title] stain

Nat Pernick, M.D.
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Cite this page: Pernick N. Human papillomavirus. website. Accessed January 24th, 2021.
Definition / 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
Microscopic (histologic) images

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Anal squamous neoplasia, HPV L1 capsid

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Cervix, normal

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Cervical condyloma

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Cervix, low grade SIL

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Cervix, high grade SIL

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Cervix, squamous cell carcinoma

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Cervix, large cell neuroendo carcinoma

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Eye, conjunctival tumors

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Oropharyngeal squamous cell carcinoma, HPV ISH and p16

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 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
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