+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Serial measurement of type-specific human papillomavirus load enables classification of cervical intraepithelial neoplasia lesions according to occurring human papillomavirus-induced pathway



Serial measurement of type-specific human papillomavirus load enables classification of cervical intraepithelial neoplasia lesions according to occurring human papillomavirus-induced pathway



European Journal of Cancer Prevention 26(2): 156-164



This retrospective study examined whether human papillomavirus (HPV) type-specific viral load changes measured in two or three serial cervical smears are predictive for the natural evolution of HPV infections and correlate with histological grades of cervical intraepithelial neoplasia (CIN), allowing triage of HPV-positive women. A cervical histology database was used to select consecutive women with biopsy-proven CIN in 2012 who had at least two liquid-based cytology samples before the diagnosis of CIN. Before performing cytology, 18 different quantitative PCRs allowed HPV type-specific viral load measurement. Changes in HPV-specific load between measurements were assessed by linear regression, with calculation of coefficient of determination (R) and slope. All infections could be classified into one of five categories: (i) clonal progressing process (R≥0.85; positive slope), (ii) simultaneously occurring clonal progressive and transient infection, (iii) clonal regressing process (R≥0.85; negative slope), (iv) serial transient infection with latency [R<0.85; slopes (two points) between 0.0010 and -0.0010 HPV copies/cell/day], and (v) transient productive infection (R<0.85; slope: ±0.0099 HPV copies/cell/day). Three hundred and seven women with CIN were included; 124 had single-type infections and 183 had multiple HPV types. Only with three consecutive measurements could a clonal process be identified in all CIN3 cases. We could clearly demonstrate clonal regressing lesions with a persistent linear decrease in viral load (R≥0.85; -0.003 HPV copies/cell/day) in all CIN categories. Type-specific viral load increase/decrease in three consecutive measurements enabled classification of CIN lesions in clonal HPV-driven transformation (progression/regression) and nonclonal virion-productive (serial transient/transient) processes.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058831406

Download citation: RISBibTeXText

PMID: 26890987

DOI: 10.1097/cej.0000000000000241


Related references

Serial type-specific human papillomavirus (HPV) load measurement allows differentiation between regressing cervical lesions and serial virion productive transient infections. Cancer Medicine 4(8): 1294-1302, 2015

Human papillomavirus L1 capsid protein and human papillomavirus type 16 as prognostic markers in cervical intraepithelial neoplasia 1. International Journal of Gynecological Cancer 20(2): 288-293, 2010

Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2-3. Journal of the National Cancer Institute 101(3): 153-161, 2009

Effect of cervical cytologic status on the association between human papillomavirus type 16 DNA load and the risk of cervical intraepithelial neoplasia grade 3. Journal of Infectious Diseases 198(3): 324-331, 2008

Human papillomavirus detection in cervical lesions nondiagnostic for cervical intraepithelial neoplasia: correlation with Papanicolaou smear, colposcopy, and occurrence of cervical intraepithelial neoplasia. Obstetrics and Gynecology 75(6): 1006-1011, 1990

Determinants of human papillomavirus load among women with histological cervical intraepithelial neoplasia 3: dominant impact of surrounding low-grade lesions. Cancer Epidemiology Biomarkers and Prevention 12(10): 1038-1044, 2003

Type-specific human papillomavirus prevalence in cervical intraepithelial neoplasia and cancer in Iran. Journal of Medical Virology 90(1): 172-176, 2018

Conization for cervical intraepithelial neoplasia is followed by disappearance of human papillomavirus deoxyribonucleic acid and a decline in serum and cervical mucus antibodies against human papillomavirus antigens. American Journal Of Obstetrics & Gynecology. 174(3): 937-942, 1996

Changes in the physical state and expression of human papillomavirus type 16 in the progression of cervical intraepithelial neoplasia lesions analysed by PCR. Journal of General Virology 76: 2589-2593, 1995

Human papillomavirus type 16 causes larger colposcopic lesions than other HPV types in patients with grade 3 cervical intraepithelial neoplasia. Journal of Lower Genital Tract Disease 17(1): 1-5, 2013

Human papillomavirus type 16 E2-specific T-helper lymphocyte responses in patients with cervical intraepithelial neoplasia. Journal of General Virology 80: 2453-2459, 1999

Human papillomavirus preceding intraepithelial neoplasia in serial cervical smears. Lancet 1(8592): 989, 1988

Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia. Immunology 119(4): 507-514, 2006

Low-risk human papillomavirus type 6 DNA load and integration in cervical samples from women with squamous intraepithelial lesions. Journal of Clinical Virology 45(2): 96-99, 2009

Type-specific human papillomavirus DNA in abnormal smears as a predictor of high-grade cervical intraepithelial neoplasia. British Journal of Cancer 69(1): 167-171, 1994