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Published in: Virology Journal 1/2013

Open Access 01-12-2013 | Research

Detection of specific HPV subtypes responsible for the pathogenesis of condylomata acuminata

Authors: Matthew G Hawkins, David M Winder, Siolian LR Ball, Katie Vaughan, Christopher Sonnex, Margaret A Stanley, Jane C Sterling, Peter KC Goon

Published in: Virology Journal | Issue 1/2013

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Abstract

Background

The low-risk human papillomavirus types 6 and 11 are responsible for approximately 90% of anogenital wart cases, with approximately 190,000 new and recurrent cases reported in the UK in 2010. The UK has recently selected the quadrivalent HPV vaccine, which conveys protection against both HPV6 and HPV 11, as part of its immunisation programme for 2012 and it is expected that this will reduce disease burden in the UK. The aims of the study were to evaluate current strategies used for the monitoring of HPV infection in genital warts and to assess the suitability of laser-capture microdissection (LCM) as a technique to improve the understanding of the natural history of HPV types associated with genital wart lesions.

Methods

DNA and RNA were extracted from whole wart, surface swabs and LCM sections from 23 patients. HPV types present were determined using the Linear Array HPV Genotyping Test (Roche), with HPV DNA viral load and mRNA expression investigated using qPCR and qRT-PCR, respectively.

Results

Results indicated that swabbing the surface of warts does not accurately reflect potential causative HPV types present within a wart lesion, multiple HPV types being present on the surface of the wart that are absent in the lower layers of tissue isolated by LCM. Although it was shown that HPV DNA viral load does not directly correlate with HPV mRNA load, the presence of both DNA and mRNA from a single HPV type suggested a causative role in lesion development in 8/12 (66.6%) of patients analysed, with dual infections seen in 4/12 (33.3%) cases. HPV 6 and HPV 11 were present in more than 90% of the lesions examined.

Conclusions

Surface swabbing of warts does not necessarily reflect the causative HPV types. HPV type specific DNA and mRNA loads do not correlate. HPV 6 and 11 were likely to be causally involved in over 90% of the lesions. Dual infections were also found, and further studies are required to determine the biological and clinical nature of dual/multiple infections and to establish the relationship of multiple HPV types within a single lesion.
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Literature
1.
go back to reference Lanitis T, Carroll S, O'Mahony C, Charman F, Khalid JM, Griffiths V, Brown RE: The cost of managing genital warts in the UK. Int J STD AIDS 2012, 23: 189-194. 10.1258/ijsa.2011.011218PubMedCrossRef Lanitis T, Carroll S, O'Mahony C, Charman F, Khalid JM, Griffiths V, Brown RE: The cost of managing genital warts in the UK. Int J STD AIDS 2012, 23: 189-194. 10.1258/ijsa.2011.011218PubMedCrossRef
2.
go back to reference Lacey CJ: Therapy for genital human papillomavirus-related disease. J Clin Virol 2005,32(Suppl 1):S82-S90.PubMedCrossRef Lacey CJ: Therapy for genital human papillomavirus-related disease. J Clin Virol 2005,32(Suppl 1):S82-S90.PubMedCrossRef
3.
go back to reference Donovan B, Franklin N, Guy R, Grulich AE, Regan DG, Ali H, Wand H, Fairley CK: Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis 2011, 11: 39-44. 10.1016/S1473-3099(10)70225-5PubMedCrossRef Donovan B, Franklin N, Guy R, Grulich AE, Regan DG, Ali H, Wand H, Fairley CK: Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis 2011, 11: 39-44. 10.1016/S1473-3099(10)70225-5PubMedCrossRef
4.
go back to reference Baldwin SB, Wallace DR, Papenfuss MR, Abrahamsen M, Vaught LC, Kornegay JR, Hallum JA, Redmond SA, Giuliano AR: Human papillomavirus infection in men attending a sexually transmitted disease clinic. J Infect Dis 2003, 187: 1064-1070. 10.1086/368220PubMedCrossRef Baldwin SB, Wallace DR, Papenfuss MR, Abrahamsen M, Vaught LC, Kornegay JR, Hallum JA, Redmond SA, Giuliano AR: Human papillomavirus infection in men attending a sexually transmitted disease clinic. J Infect Dis 2003, 187: 1064-1070. 10.1086/368220PubMedCrossRef
5.
go back to reference Cui MH, Liu YQ, Li HL, Li SR: Human papillomavirus in condyloma acuminata and other benign lesions of the female genital tract. Chin Med J (Engl) 1994, 107: 703-708. Cui MH, Liu YQ, Li HL, Li SR: Human papillomavirus in condyloma acuminata and other benign lesions of the female genital tract. Chin Med J (Engl) 1994, 107: 703-708.
6.
go back to reference Muller EE, Chirwa TF, Lewis DA: Human papillomavirus (HPV) infection in heterosexual South African men attending sexual health services: associations between HPV and HIV serostatus. Sex Transm Infect 2009, 86: 175-180.PubMedCrossRef Muller EE, Chirwa TF, Lewis DA: Human papillomavirus (HPV) infection in heterosexual South African men attending sexual health services: associations between HPV and HIV serostatus. Sex Transm Infect 2009, 86: 175-180.PubMedCrossRef
7.
go back to reference Vajdic CM, van Leeuwen MT, Jin F, Prestage G, Medley G, Hillman RJ, Stevens MP, Botes LP, Zablotska I, Tabrizi SN, Grulich AE: Anal human papillomavirus genotype diversity and co-infection in a community-based sample of homosexual men. Sex Transm Infect 2009, 85: 330-335. 10.1136/sti.2008.034744PubMedCrossRef Vajdic CM, van Leeuwen MT, Jin F, Prestage G, Medley G, Hillman RJ, Stevens MP, Botes LP, Zablotska I, Tabrizi SN, Grulich AE: Anal human papillomavirus genotype diversity and co-infection in a community-based sample of homosexual men. Sex Transm Infect 2009, 85: 330-335. 10.1136/sti.2008.034744PubMedCrossRef
8.
go back to reference Ball SL, Winder DM, Vaughan K, Hanna N, Levy J, Sterling JC, Stanley MA, Goon PK: Analyses of human papillomavirus genotypes and viral loads in anogenital warts. J Med Virol 2011, 83: 1345-1350. 10.1002/jmv.22111PubMedCrossRef Ball SL, Winder DM, Vaughan K, Hanna N, Levy J, Sterling JC, Stanley MA, Goon PK: Analyses of human papillomavirus genotypes and viral loads in anogenital warts. J Med Virol 2011, 83: 1345-1350. 10.1002/jmv.22111PubMedCrossRef
9.
go back to reference Brown DR, Schroeder JM, Bryan JT, Stoler MH, Fife KH: Detection of multiple human papillomavirus types in Condylomata acuminata lesions from otherwise healthy and immunosuppressed patients. J Clin Microbiol 1999, 37: 3316-3322.PubMedPubMedCentral Brown DR, Schroeder JM, Bryan JT, Stoler MH, Fife KH: Detection of multiple human papillomavirus types in Condylomata acuminata lesions from otherwise healthy and immunosuppressed patients. J Clin Microbiol 1999, 37: 3316-3322.PubMedPubMedCentral
10.
go back to reference Chan PK, Luk AC, Luk TN, Lee KF, Cheung JL, Ho KM, Lo KK: Distribution of human papillomavirus types in anogenital warts of men. J Clin Virol 2009, 44: 111-114. 10.1016/j.jcv.2008.11.001PubMedCrossRef Chan PK, Luk AC, Luk TN, Lee KF, Cheung JL, Ho KM, Lo KK: Distribution of human papillomavirus types in anogenital warts of men. J Clin Virol 2009, 44: 111-114. 10.1016/j.jcv.2008.11.001PubMedCrossRef
11.
go back to reference Quint W, Jenkins D, Molijn A, Struijk L, van de Sandt M, Doorbar J, Mols J, Van Hoof C, Hardt K, Struyf F, Colau B: One virus, one lesion–individual components of CIN lesions contain a specific HPV type. J Pathol 2012, 227: 62-71. 10.1002/path.3970PubMedCrossRef Quint W, Jenkins D, Molijn A, Struijk L, van de Sandt M, Doorbar J, Mols J, Van Hoof C, Hardt K, Struyf F, Colau B: One virus, one lesion–individual components of CIN lesions contain a specific HPV type. J Pathol 2012, 227: 62-71. 10.1002/path.3970PubMedCrossRef
12.
go back to reference Cattani P, Siddu A, D'Onghia S, Marchetti S, Santangelo R, Vellone VG, Zannoni GF, Fadda G: RNA (E6 and E7) assays versus DNA (E6 and E7) assays for risk evaluation for women infected with human papillomavirus. J Clin Microbiol 2009, 47: 2136-2141. 10.1128/JCM.01733-08PubMedPubMedCentralCrossRef Cattani P, Siddu A, D'Onghia S, Marchetti S, Santangelo R, Vellone VG, Zannoni GF, Fadda G: RNA (E6 and E7) assays versus DNA (E6 and E7) assays for risk evaluation for women infected with human papillomavirus. J Clin Microbiol 2009, 47: 2136-2141. 10.1128/JCM.01733-08PubMedPubMedCentralCrossRef
13.
go back to reference Gnanamony M, Peedicayil A, Subhashini J, Ram TS, Christopher S, Gravitt P, Abraham P: Human papillomavirus types 16 and 18 mRNA levels and not DNA levels may be associated with advancing stages of cervical cancer. Int J Gynecol Cancer 2009, 19: 1415-1420. 10.1111/IGC.0b013e3181b62e05PubMedCrossRef Gnanamony M, Peedicayil A, Subhashini J, Ram TS, Christopher S, Gravitt P, Abraham P: Human papillomavirus types 16 and 18 mRNA levels and not DNA levels may be associated with advancing stages of cervical cancer. Int J Gynecol Cancer 2009, 19: 1415-1420. 10.1111/IGC.0b013e3181b62e05PubMedCrossRef
14.
go back to reference Kosel S, Burggraf S, Engelhardt W, Olgemoller B: Increased levels of HPV16 E6*I transcripts in high-grade cervical cytology and histology (CIN II+) detected by rapid real-time RT-PCR amplification. Cytopathology 2007, 18: 290-299. 10.1111/j.1365-2303.2007.00481.xPubMedCrossRef Kosel S, Burggraf S, Engelhardt W, Olgemoller B: Increased levels of HPV16 E6*I transcripts in high-grade cervical cytology and histology (CIN II+) detected by rapid real-time RT-PCR amplification. Cytopathology 2007, 18: 290-299. 10.1111/j.1365-2303.2007.00481.xPubMedCrossRef
15.
16.
go back to reference Blomberg M, Friis S, Munk C, Bautz A, Kjaer SK: Genital warts and risk of cancer: a danish study of nearly 50 000 patients with genital warts. J Infect Dis 2012, 205: 1544-1553. 10.1093/infdis/jis228PubMedCrossRef Blomberg M, Friis S, Munk C, Bautz A, Kjaer SK: Genital warts and risk of cancer: a danish study of nearly 50 000 patients with genital warts. J Infect Dis 2012, 205: 1544-1553. 10.1093/infdis/jis228PubMedCrossRef
17.
go back to reference Lacey CJ, Lowndes CM, Shah KV: Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine 2006,24(3):35-41.CrossRef Lacey CJ, Lowndes CM, Shah KV: Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine 2006,24(3):35-41.CrossRef
18.
go back to reference Hadjivassiliou M, Stefanaki C, Nicolaidou E, Bethimoutis G, Anyfantakis V, Caroni C, Katsambas A: Human papillomavirus assay in genital warts–correlation with symptoms. Int J STD AIDS 2007, 18: 329-334. 10.1258/095646207780749574PubMedCrossRef Hadjivassiliou M, Stefanaki C, Nicolaidou E, Bethimoutis G, Anyfantakis V, Caroni C, Katsambas A: Human papillomavirus assay in genital warts–correlation with symptoms. Int J STD AIDS 2007, 18: 329-334. 10.1258/095646207780749574PubMedCrossRef
19.
go back to reference Hillman RJ, Botcherby M, Ryait BK, Hanna N, Taylor-Robinson D: Detection of human papillomavirus DNA in the urogenital tracts of men with anogenital warts. Sex Transm Dis 1993, 20: 21-27. 10.1097/00007435-199301000-00005PubMedCrossRef Hillman RJ, Botcherby M, Ryait BK, Hanna N, Taylor-Robinson D: Detection of human papillomavirus DNA in the urogenital tracts of men with anogenital warts. Sex Transm Dis 1993, 20: 21-27. 10.1097/00007435-199301000-00005PubMedCrossRef
20.
go back to reference Stefanaki C, Hadjivassiliou M, Katzouranis I, Bethimoutis G, Nicolaidou E, Anyfantakis V, Lagogianni E, Caroni C, Panagiotopoulos A, Antoniou C, Katsambas A: Prognostic factors for the response to treatment in males with genital warts. J Eur Acad Dermatol Venereol 2009, 23: 1156-1160. 10.1111/j.1468-3083.2009.03270.xPubMedCrossRef Stefanaki C, Hadjivassiliou M, Katzouranis I, Bethimoutis G, Nicolaidou E, Anyfantakis V, Lagogianni E, Caroni C, Panagiotopoulos A, Antoniou C, Katsambas A: Prognostic factors for the response to treatment in males with genital warts. J Eur Acad Dermatol Venereol 2009, 23: 1156-1160. 10.1111/j.1468-3083.2009.03270.xPubMedCrossRef
21.
go back to reference Vandepapeliere P, Barrasso R, Meijer CJ, Walboomers JM, Wettendorff M, Stanberry LR, Lacey CJ: Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination. J Infect Dis 2005, 192: 2099-2107. 10.1086/498164PubMedCrossRef Vandepapeliere P, Barrasso R, Meijer CJ, Walboomers JM, Wettendorff M, Stanberry LR, Lacey CJ: Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination. J Infect Dis 2005, 192: 2099-2107. 10.1086/498164PubMedCrossRef
22.
go back to reference Potocnik M, Kocjan B, Seme K, Poljak M: Distribution of human papillomavirus (HPV) genotypes in genital warts from males in Slovenia. Acta Dermatovenerol Alp Panonica Adriat 2007, 16: 91-96. 98 Potocnik M, Kocjan B, Seme K, Poljak M: Distribution of human papillomavirus (HPV) genotypes in genital warts from males in Slovenia. Acta Dermatovenerol Alp Panonica Adriat 2007, 16: 91-96. 98
23.
go back to reference Al-Waiz MM, Al-Saadi RN, Al-Saadi ZA, Al-Rawi FA: Subclinical human papillomavirus infection of the cervix. Saudi Med J 2001, 22: 694-697.PubMed Al-Waiz MM, Al-Saadi RN, Al-Saadi ZA, Al-Rawi FA: Subclinical human papillomavirus infection of the cervix. Saudi Med J 2001, 22: 694-697.PubMed
24.
go back to reference Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnurch HG, zur Hausen H: Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci USA 1983, 80: 560-563. 10.1073/pnas.80.2.560PubMedPubMedCentralCrossRef Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnurch HG, zur Hausen H: Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci USA 1983, 80: 560-563. 10.1073/pnas.80.2.560PubMedPubMedCentralCrossRef
25.
go back to reference Greer CE, Wheeler CM, Ladner MB, Beutner K, Coyne MY, Liang H, Langenberg A, Yen TS, Ralston R: Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts. J Clin Microbiol 1995, 33: 2058-2063.PubMedPubMedCentral Greer CE, Wheeler CM, Ladner MB, Beutner K, Coyne MY, Liang H, Langenberg A, Yen TS, Ralston R: Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts. J Clin Microbiol 1995, 33: 2058-2063.PubMedPubMedCentral
26.
go back to reference Edwards RA: Laser capture microdissection of mammalian tissue. J Vis Exp 2007, 8: 309.PubMed Edwards RA: Laser capture microdissection of mammalian tissue. J Vis Exp 2007, 8: 309.PubMed
27.
go back to reference Winder DM, Ball SL, Vaughan K, Hanna N, Woo YL, Franzer JT, Sterling JC, Stanley MA, Sudhoff H, Goon PK: Sensitive HPV detection in oropharyngeal cancers. BMC Cancer 2009, 9: 440. 10.1186/1471-2407-9-440PubMedPubMedCentralCrossRef Winder DM, Ball SL, Vaughan K, Hanna N, Woo YL, Franzer JT, Sterling JC, Stanley MA, Sudhoff H, Goon PK: Sensitive HPV detection in oropharyngeal cancers. BMC Cancer 2009, 9: 440. 10.1186/1471-2407-9-440PubMedPubMedCentralCrossRef
28.
go back to reference Crawford R, Grignon AL, Kitson S, Winder DM, Ball SL, Vaughan K, Stanley MA, Sterling JC, Goon PK: High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology. BMC Cancer 2011, 11: 473. 10.1186/1471-2407-11-473PubMedPubMedCentralCrossRef Crawford R, Grignon AL, Kitson S, Winder DM, Ball SL, Vaughan K, Stanley MA, Sterling JC, Goon PK: High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology. BMC Cancer 2011, 11: 473. 10.1186/1471-2407-11-473PubMedPubMedCentralCrossRef
29.
go back to reference Woo YL, Damay I, Stanley M, Crawford R, Sterling J: The use of HPV Linear Array Assay for multiple HPV typing on archival frozen tissue and DNA specimens. J Virol Methods 2007, 142: 226-230. 10.1016/j.jviromet.2007.01.029PubMedCrossRef Woo YL, Damay I, Stanley M, Crawford R, Sterling J: The use of HPV Linear Array Assay for multiple HPV typing on archival frozen tissue and DNA specimens. J Virol Methods 2007, 142: 226-230. 10.1016/j.jviromet.2007.01.029PubMedCrossRef
30.
go back to reference Doorbar J: Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond) 2006, 110: 525-541.CrossRef Doorbar J: Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond) 2006, 110: 525-541.CrossRef
31.
go back to reference Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA: The biology and life-cycle of human papillomaviruses. Vaccine 2012,30(Suppl 5):F55-F70.PubMedCrossRef Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA: The biology and life-cycle of human papillomaviruses. Vaccine 2012,30(Suppl 5):F55-F70.PubMedCrossRef
33.
go back to reference Landis JR, Koch GG: The measurement of observer agreement for categorical data. Biometrics 1977, 33: 159-174. 10.2307/2529310PubMedCrossRef Landis JR, Koch GG: The measurement of observer agreement for categorical data. Biometrics 1977, 33: 159-174. 10.2307/2529310PubMedCrossRef
Metadata
Title
Detection of specific HPV subtypes responsible for the pathogenesis of condylomata acuminata
Authors
Matthew G Hawkins
David M Winder
Siolian LR Ball
Katie Vaughan
Christopher Sonnex
Margaret A Stanley
Jane C Sterling
Peter KC Goon
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-10-137

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