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Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

The DNA load of six high-risk human papillomavirus types and its association with cervical lesions

Authors: Luisa Del Río-Ospina, Sara Cecilia Soto-De León, Milena Camargo, Darwin Andrés Moreno-Pérez, Ricardo Sánchez, Antonio Pérez-Prados, Manuel Elkin Patarroyo, Manuel Alfonso Patarroyo

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Analysing human papillomavirus (HPV) viral load is important in determining the risk of developing cervical cancer (CC); most knowledge to date regarding HPV viral load and cervical lesions has been related to HPV-16. This study evaluated the association between the viral load of the six most prevalent high-risk viral types in Colombia and cervical intraepithelial neoplasia (CIN) frequency.

Methods

114 women without CIN and 59 women having CIN confirmed by colposcopy, all of them positive by conventional PCR for HPV infection in the initial screening, were included in the study. Samples were tested for six high-risk HPV types to determine viral copy number by real-time PCR. Crude and adjusted odds ratios (ORa) were estimated for evaluating the association between each viral type’s DNA load and the risk of cervical lesions occurring.

Results

The highest viral loads were identified for HPV-33 in CIN patients and for HPV-31 in patients without lesions (9.33 HPV copies, 2.95 interquartile range (IQR); 9.41 HPV copies, 2.58 IQR). Lesions were more frequent in HPV-16 patients having a low viral load (3.53 ORa, 1.16–10.74 95%CI) compared to those having high HPV-16 load (2.62 ORa, 1.08–6.35 95%CI). High viral load in HPV-31 patients was associated with lower CIN frequency (0.34 ORa, 0.15–0.78 95%CI).

Conclusions

An association between HPV DNA load and CIN frequency was seen to be type-specific and may have depended on the duration of infection. This analysis has provided information for understanding the effect of HPV DNA load on cervical lesion development.
Literature
1.
Ault KA. Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol. 2006;2006(Suppl):1–5.CrossRef
2.
Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348:518–27.CrossRefPubMed
3.
Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer. 2011;128:927–35.CrossRefPubMed
4.
de Freitas AC, Gurgel AP, Chagas BS, Coimbra EC, Do Amaral CM. Susceptibility to cervical cancer: an overview. Gynecol Oncol. 2012;126:304–11.CrossRefPubMed
5.
6.
Munoz N, Hernandez-Suarez G, Mendez F, Molano M, Posso H, Moreno V, et al. Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women. Br J Cancer. 2009;100:1184–90.CrossRefPubMedPubMedCentral
7.
Ramanakumar AV, Goncalves O, Richardson H, Tellier P, Ferenczy A, Coutlee F, et al. Human papillomavirus (HPV) types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women. BMC Infect Dis. 2010;10:326.CrossRefPubMedPubMedCentral
8.
Hernández-Hernández DM, Ornelas-Bernal L, Guido-Jiménez M, Apresa-Garcia T, Alvarado-Cabrero I, Salcedo-Vargas M, et al. Association between high-risk human papillomavirus DNA load and precursor lesions of cervical cancer in Mexican women. Gynecol Oncol. 2003;90:310–7.CrossRefPubMed
9.
Josefsson AM, Magnusson PK, Ylitalo N, Sorensen P, Qwarforth-Tubbin P, Andersen PK, et al. Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case–control study. Lancet. 2000;355:2189–93.CrossRefPubMed
10.
Moberg M, Gustavsson I, Wilander E, Gyllensten U. High viral loads of human papillomavirus predict risk of invasive cervical carcinoma. Br J Cancer. 2005;92:891–4.CrossRefPubMedPubMedCentral
11.
Ylitalo N, Sorensen P, Josefsson AM, Magnusson PK, Andersen PK, Ponten J, et al. Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case–control study. Lancet. 2000;355:2194–8.CrossRefPubMed
12.
Andersson S, Safari H, Mints M, Lewensohn-Fuchs I, Gyllensten U, Johansson B. Type distribution, viral load and integration status of high-risk human papillomaviruses in pre-stages of cervical cancer (CIN). Br J Cancer. 2005;92:2195–200.CrossRefPubMedPubMedCentral
13.
Moberg M, Gustavsson I, Gyllensten U. Real-time PCR-based system for simultaneous quantification of human papillomavirus types associated with high risk of cervical cancer. J Clin Microbiol. 2003;41:3221–8.CrossRefPubMedPubMedCentral
14.
Sherman ME, Schiffman M, Cox JT, Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study G. Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). J Natl Cancer Inst. 2002;94:102–7.CrossRefPubMed
15.
Carcopino X, Henry M, Mancini J, Giusiano S, Boubli L, Olive D, et al. Significance of HPV 16 and 18 viral load quantitation in women referred for colposcopy. J Med Virol. 2012;84:306–13.CrossRefPubMed
16.
Swan DC, Tucker RA, Tortolero-Luna G, Mitchell MF, Wideroff L, Unger ER, et al. Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type. J Clin Microbiol. 1999;37:1030–4.PubMedPubMedCentral
17.
Jenkins A, Allum AG, Strand L, Aakre RK. Simultaneous detection, typing and quantitation of oncogenic human papillomavirus by multiplex consensus real-time PCR. J Virol Methods. 2013;187:345–51.CrossRefPubMed
18.
Schmitt M, Depuydt C, Benoy I, Bogers J, Antoine J, Pawlita M, et al. Viral load of high-risk human papillomaviruses as reliable clinical predictor for the presence of cervical lesions. Cancer Epidemiol Biomarkers Prev. 2013;22:406–14.CrossRefPubMed
19.
Camargo M, Soto-De Leon SC, Sanchez R, Perez-Prados A, Patarroyo ME, Patarroyo MA. Frequency of human papillomavirus infection, coinfection, and association with different risk factors in Colombia. Ann Epidemiol. 2011;21:204–13.CrossRefPubMed
20.
Ramírez VG, Bustamante MA, Sarmiento CA. Norma Técnica para la Detección Temprana del Cáncer de Cuello Uterino y Guía de Atención de Lesiones Preneoplásicas de Cuello Uterino. Colombia: Ministerio de Salud, Dirección General de Promoción y Prevenció; 2000. p. 1–26.
21.
Rijkaart DC, Berkhof J, van Kemenade FJ, Coupe VM, Rozendaal L, Heideman DA, et al. HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications. Br J Cancer. 2012;106:975–81.CrossRefPubMedPubMedCentral
22.
Sellors J, Sankaranarayanan R. La colposcopia y el tratamiento de la neoplasia intraepitelial cervical: Manual para principiantes. Lyon, Francia: International Agency for Research on Cancer (IARC); 2003. p. 140.
23.
Boicea A, Patrascu A, Surlin V, Iliescu D, Schenker M, Chiutu L. Correlations between colposcopy and histologic results from colposcopically directed biopsy in cervical precancerous lesions. Rom J Leg Med. 2012;53:735–41.
24.
Kitchener HC, Castle PE, Cox JT. Chapter 7: Achievements and limitations of cervical cytology screening. Vaccine. 2006;24 Suppl 3:S3/63–70.
25.
Cronje HS, Cooreman BF, Beyer E, Bam RH, Middlecote BD, Divall PD. Screening for cervical neoplasia in a developing country utilizing cytology, cervicography and the acetic acid test. Int J Gynecol Obstet. 2001;72:151–7.CrossRef
26.
Cronje HS, Parham GP, Cooreman BF, de Beer A, Divall P, Bam RH. A comparison of four screening methods for cervical neoplasia in a developing country. Am J Obstet Gynecol. 2003;188:395–400.CrossRefPubMed
27.
Soto-De Leon S, Camargo M, Sanchez R, Munoz M, Perez-Prados A, Purroy A, et al. Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors. PLoS One. 2011;6:e14705.CrossRefPubMedPubMedCentral
28.
Soto-De Leon SC, Del Rio-Ospina L, Camargo M, Sanchez R, Moreno-Perez DA, Perez-Prados A, et al. Persistence, clearance and reinfection regarding six high risk human papillomavirus types in Colombian women: a follow-up study. BMC Infect Dis. 2014;14:395.CrossRefPubMedPubMedCentral
29.
Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22:4673–80.CrossRefPubMedPubMedCentral
30.
Wu Y, Chen Y, Li L, Yu G, Zhang Y, He Y. Associations of high-risk HPV types and viral load with cervical cancer in China. J Clin Virol. 2006;35:264–9.CrossRefPubMed
31.
Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, et al. The 2001 Bethesda system: terminology for reporting results of cervical cytology. JAMA. 2001;2002(287):2114–9.
32.
Broutet N, Dangou JM, Fadhil I, Lazdane G, Luciani S, Mathur A, et al. WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. South Africa: World Health Organization; 2013. p. 1–60.
33.
Monnier-Benoit S, Dalstein V, Riethmuller D, Lalaoui N, Mougin C, Pretet JL. Dynamics of HPV16 DNA load reflect the natural history of cervical HPV-associated lesions. J Clin Virol. 2006;35:270–7.CrossRefPubMed
34.
Moore RA, Ogilvie G, Fornika D, Moravan V, Brisson M, Amirabbasi-Beik M, et al. Prevalence and type distribution of human papillomavirus in 5,000 British Columbia women–implications for vaccination. Cancer Causes Control. 2009;20:1387–96.CrossRefPubMedPubMedCentral
35.
Guan P, Howell-Jones R, Li N, Bruni L, de Sanjose S, Franceschi S, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131:2349–59.CrossRefPubMed
36.
Poljak M, Seme K, Maver PJ, Kocjan BJ, Cuschieri KS, Rogovskaya SI, et al. Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Central and Eastern Europe. Vaccine. 2013;31 Suppl 7:H59–70.CrossRefPubMed
37.
Cuschieri KS, Cubie HA, Whitley MW, Seagar AL, Arends MJ, Moore C, et al. Multiple high risk HPV infections are common in cervical neoplasia and young women in a cervical screening population. J Clin Pathol. 2004;57:68–72.CrossRefPubMedPubMedCentral
38.
Garcia DA, Cid-Arregui A, Schmitt M, Castillo M, Briceno I, Aristizabal FA. Highly sensitive detection and genotyping of HPV by PCR multiplex and luminex technology in a cohort of colombian women with abnormal cytology. Open Virol J. 2011;5:70–9.CrossRefPubMedPubMedCentral
39.
Xi LF, Hughes JP, Edelstein ZR, Kiviat NB, Koutsky LA, Mao C, et al. Human Papillomavirus (HPV) type 16 and type 18 DNA Loads at Baseline and Persistence of Type-Specific Infection during a 2-year follow-up. J Infect Dis. 2009;200:1789–97.CrossRefPubMedPubMedCentral
40.
Schmitt M, Depuydt C, Benoy I, Bogers J, Antoine J, Arbyn M, et al. Multiple human papillomavirus infections with high viral loads are associated with cervical lesions but do not differentiate grades of cervical abnormalities. J Clin Microbiol. 2013;51:1458–64.CrossRefPubMedPubMedCentral
41.
42.
Zerbini M, Venturoli S, Cricca M, Gallinella G, De Simone P, Costa S, et al. Distribution and viral load of type specific HPVs in different cervical lesions as detected by PCR-ELISA. J Clin Pathol. 2001;54:377–80.CrossRefPubMedPubMedCentral
43.
Manawapat A, Stubenrauch F, Russ R, Munk C, Kjaer SK, Iftner T. Physical state and viral load as predictive biomarkersfor persistence and progression of HPV16-positive cervical lesions: results from a population based long-term prospective cohort study. Am J Cancer Res. 2012;2:192–203.PubMedPubMedCentral
44.
Winer RL, Xi LF, Shen Z, Stern JE, Newman L, Feng Q, et al. Viral load and short-term natural history of type-specific oncogenic human papillomavirus infections in a high-risk cohort of midadult women. Int J Cancer. 2014;134:1889–98.CrossRefPubMed
45.
Kulmala SM, Syrjanen SM, Gyllensten UB, Shabalova IP, Petrovichev N, Tosi P, et al. Early integration of high copy HPV16 detectable in women with normal and low grade cervical cytology and histology. J Clin Pathol. 2006;59:513–7.CrossRefPubMedPubMedCentral
46.
Nakagawa M, Stites DP, Patel S, Farhat S, Scott M, Hills NK, et al. Persistence of human papillomavirus type 16 infection is associated with lack of cytotoxic T lymphocyte response to the E6 antigens. J Infect Dis. 2000;182:595–8.CrossRefPubMed
47.
Brenna SM, Syrjanen KJ. Regulation of cell cycles is of key importance in human papillomavirus (HPV)-associated cervical carcinogenesis. Sao Paulo Med J. 2003;121:128–32.CrossRefPubMed
48.
van Duin M, Snijders PJ, Schrijnemakers HF, Voorhorst FJ, Rozendaal L, Nobbenhuis MA, et al. Human papillomavirus 16 load in normal and abnormal cervical scrapes: an indicator of CIN II/III and viral clearance. Int J Cancer. 2002;98:590–5.CrossRefPubMed
49.
Chan PK, Cheung JL, Cheung TH, Lo KW, Yim SF, Siu SS, et al. Profile of viral load, integration, and E2 gene disruption of HPV58 in normal cervix and cervical neoplasia. J Infect Dis. 2007;196:868–75.CrossRefPubMed
50.
Gravitt PE, Kovacic MB, Herrero R, Schiffman M, Bratti C, Hildesheim A, et al. High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease. Int J Cancer. 2007;121:2787–93.CrossRefPubMedPubMedCentral
51.
Moberg M, Gustavsson I, Gyllensten U. Type-specific associations of human papillomavirus load with risk of developing cervical carcinoma in situ. Int J Cancer. 2004;112:854–9.CrossRefPubMed
Metadata
Title
The DNA load of six high-risk human papillomavirus types and its association with cervical lesions
Authors
Luisa Del Río-Ospina
Sara Cecilia Soto-De León
Milena Camargo
Darwin Andrés Moreno-Pérez
Ricardo Sánchez
Antonio Pérez-Prados
Manuel Elkin Patarroyo
Manuel Alfonso Patarroyo
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1126-z

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