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Atypia / premalignant / preinvasive lesions

Human papilloma virus (HPV)

Reviewer: Marilin Rosa, M.D., University of Florida (see Reviewers page)
Revised: 6 May 2014, last major update May 2011
Copyright: (c) 2006-2011, PathologyOutlines.com, Inc.

See also HPV testing


Koilocytosis / koilocytotic atypia: 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


● Koilocytic changes are classified as Low grade squamous intraepithelial lesion (LSIL) in the new Bethesda terminology (Solomon: The Bethesda System for Reporting Cervical Cytology;2005 (2nd ed))


● 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 200x 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, click here

HPV testing

● Triage ASCUS or LSIL cases (HPV+ are more likely to have HSIL at followup); confirm cervical origin of squamous cell carcinoma or adenocarcinoma (Am J Clin Path 2005;124:24, Arch Pathol Lab Med 2001;125:1453)

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


Not HPV - reactive halos, contributed by: Dr. Marilin Rosa, University of Florida (USA)

Positive stains

● Ki-67 (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 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

End of Cervix-cytology > Atypia / premalignant / preinvasive lesions > Human papilloma virus (HPV)

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