Human papillomavirus (HPV) genotyping using paired exfoliated cervicovaginal cells and paraffin-embedded tissues to highlight difficulties in attributing HPV types to specific lesions.
Defining type-specific human papillomavirus (HPV) infections within cervical tissues is important for understanding the pathogenesis of cervical neoplasia and assessing the effectiveness of prophylactic vaccines with limited type-specific spectra. We compared HPV DNA-testing results from 146 matched exfoliated-cell and formalin-fixed-tissue specimens collected by cervicovaginal lavage (CVL) within 90 days of each other from women with histologically confirmed cervical intraepithelial lesions (CIN). The CVL specimens were HPV typed using a MY09/11 L1 consensus primer PCR method followed by dot blot hybridization. The tissue specimens were HPV typed using an SPF(10) line probe assay HPV detection system. Of the 146 specimen pairs with evidence of CIN in the tissue, 91.8% were positive for one or more HPV types in both the tissue and cellular specimens. Tissue sections were more likely to be HPV negative (P < 0.01). Typing directly from tissue sections resolved multiple infections detected in exfoliated cells to a single HPV type in only 46.9% of cases. Combined use of both specimen types to attribute lesions to HPV type 16 (HPV-16) and/or -18 led to 43.1% attributed to HPV-16 and/or -18 by both specimen types and 19.9% attributed to HPV-16 and/or -18 by one, but not both, specimen types. Unambiguous attribution of cervical lesions to a single, specific HPV type remains a difficult proposition. Use of multiple specimen types or the development of highly sensitive and robust in situ hybridization HPV-testing methods to evaluate the certainty of attribution of lesions to HPV types might provide insights in future efforts, including HPV vaccine trials.
Gravitt
Patti E
PE
Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Room E6535, Baltimore, MD 21205, USA. pgravitt@jhsph.edu
van Doorn
Leen Jan
LJ
Quint
Wim
W
Schiffman
Mark
M
Hildesheim
Allan
A
Glass
Andrew G
AG
Rush
Brenda B
BB
Hellman
Jared
J
Sherman
Mark E
ME
Burk
Robert D
RD
Wang
Sophia S
SS
D002584:Cervix Uteri / Q000821:virology*; D005260:Female; D005838:Genotype; D006801:Humans; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D016612:Paraffin Embedding; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D014621:Vagina / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*
J Clin Microbiol. 2000 Jan;38(1):357-61
10618116
Am J Obstet Gynecol. 2006 Aug;195(2):349-53
16677597
J Pathol. 2001 May;194(1):51-8
11329141
J Natl Cancer Inst. 2002 Jan 16;94(2):102-7
11792748
J Clin Microbiol. 2002 Mar;40(3):979-83
11880426
J Med Virol. 2002 Nov;68(3):417-23
12226831
J Natl Cancer Inst. 2003 Jan 1;95(1):46-52
12509400
N Engl J Med. 2003 Feb 6;348(6):518-27
12571259
Cancer Epidemiol Biomarkers Prev. 2003 Feb;12(2):114-9
12582020
Am J Obstet Gynecol. 1989 Dec;161(6 Pt 1):1669-72
2557764
Am J Pathol. 1998 Dec;153(6):1731-9
9846964
J Natl Cancer Inst. 1999 Jun 2;91(11):954-60
10359548
J Clin Microbiol. 1999 Aug;37(8):2508-17
10405393
Clin Cancer Res. 2005 Jul 1;11(13):4717-23
16000566
Lancet. 2006 Apr 15;367(9518):1247-55
16631880
J Virol Methods. 2001 Feb;91(2):109-17
11164492