Atypia / premalignant / preinvasive lesions
Human papilloma virus (HPV)

Topic Completed: 1 May 2011

Minor changes: 26 March 2020

Copyright: 2006-2020, PathologyOutlines.com, Inc.

PubMed search: cytology cervix Human papilloma virus (HPV) premalignant [title]

Marilin Rosa, M.D.
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Cite this page: Rosa M. Human papilloma virus (HPV). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixcytologyHPV.html. Accessed May 28th, 2020.
Definition / general
  • Koilocytosis / koilocytotic atypic: related to expression of viral E4 protein and disruption that this causes in cytoplasmic keratin matrix
  • Nuclear changes are required for diagnosis of koilocytosis since nuclear halos may be cause by glycogen accumulation (Arch Pathol Lab Med 1990;114:1038)
  • Note: perinuclear halos (reactive) can also be prominent in postmenopausal cervix without HPV
  • Most newly acquired HPV infections clear spontaneously; prevalence of HPV positivity peaks in teens and women in their 20's, then declines ( J Low Genit Tract Dis 2007;11:201)
Clinical features
  • Low risk HPV subtypes: 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, CP6108 (associated with genital condylomas and low grade SIL)
  • High risk HPV subtypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82 (associated with high grade SIL and invasive carcinoma)
  • HPV 26, 53 and 66 are probably high-risk ( Low Genit Tract Dis 2005;9:154)
  • HPV 18: associated with lesions of glandular origin, small cell neuroendocrine carcinoma
  • Presence of HPV 16 or 18 confers a 200× relative risk for HSIL for 2 years after first detection ( Eur J Obstet Gynecol Reprod Biol 2006;125:114)
  • Algorithm for HPV testing for HPV high risk positive women age 30 years+ who are cytology negative
HPV testing
Cytology description
  • Koilocytes are superficial or intermediate squamous cells with large and irregular, well defined perinuclear halos with a cookie cutter border and cytoplasmic thickening; nuclei are enlarged (two to three times normal size) with undulating (raisin-like) nuclear membrane and rope-like chromatin
  • Often bi or multinucleated with variation in nuclear size
Cytology images

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Not HPV reactive halos

Positive stains
  • Ki67 (higher in HPV+ epithelium than inflamed or metaplastic squamous epithelium (very high with high risk HPV types)
  • Diffuse and strong p16 is associated with high risk HPV (Am J Surg Pathol 2007;31:33)
Molecular / cytogenetics description
  • Two FDA approved methodologies to detect high risk HPV on cervical cytology are available today: Hybrid Capture® 2 HPV DNA Assay and Cervista™ HPV HR and Cervista™ HPV 16/18
  • Hybrid Capture® 2 HPV DNA Assay detects HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68
  • Cervista™ HPV HR detects all HPV types detected by Hybrid Capture® 2 HPV DNA Assay plus HPV 66
  • Cervista™ HPV 16/18 specifically detects HPV 16 and HPV 18
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