Performance of an HPV 16/18 E6 oncoprotein test for detection of cervical precancer and cancer.
Adult
DNA, Viral
/ genetics
DNA-Binding Proteins
/ genetics
Early Detection of Cancer
/ methods
Female
Genotype
Humans
Middle Aged
Oncogene Proteins, Viral
/ genetics
Papillomaviridae
/ classification
Papillomavirus Infections
/ diagnosis
Polymerase Chain Reaction
/ methods
Precancerous Conditions
/ diagnosis
Repressor Proteins
/ genetics
Sensitivity and Specificity
Uterine Cervical Neoplasms
/ diagnosis
Uterine Cervical Dysplasia
/ diagnosis
E6 oncoproteins
ESTAMPA
HPV
Honduras
screening
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 10 2019
15 10 2019
Historique:
received:
02
08
2018
revised:
23
11
2018
accepted:
20
12
2018
pubmed:
27
1
2019
medline:
6
2
2020
entrez:
27
1
2019
Statut:
ppublish
Résumé
HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV-tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow-up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18-related HSIL+ was 96.8% (95%CI = 83.8-99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3-68.6). Specificity was 97.5% (95%CI = 93.7-99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18-related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries.
Substances chimiques
DNA, Viral
0
DNA-Binding Proteins
0
E6 protein, Human papillomavirus type 16
0
E6 protein, Human papillomavirus type 18
0
Oncogene Proteins, Viral
0
Repressor Proteins
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2042-2050Subventions
Organisme : World Health Organization
ID : 001
Pays : International
Organisme : NCI NIH HHS
ID : UH3 CA202730
Pays : United States
Informations de copyright
© 2019 International Agency for Research on Cancer (IARC/WHO); licensed by UICC.
Références
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
Luciani S, Andrus JK. A Pan American health organization strategy for cervical cancer prevention and control in Latin America and the Caribbean. Reprod Health Matters 2008;16:59-66.
Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12-9.
zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002;2:342-50.
Boulet GA, Horvath CA, Berghmans S, et al. Human papillomavirus in cervical cancer screening: important role as biomarker. Cancer Epidemiol Biomarkers Prev 2008;17:810-7.
Cox T, Cuzick J. HPV DNA testing in cervical cancer screening: from evidence to policies. Gynecol Oncol 2006;103:8-11.
Pileggi C, Flotta D, Bianco A, et al. Is HPV DNA testing specificity comparable to that of cytological testing in primary cervical cancer screening? Results of a meta-analysis of randomized controlled trials. Int J Cancer 2014;135:166-77.
Molden T, Kraus I, Karlsen F, et al. Comparison of human papillomavirus messenger RNA and DNA detection: a cross-sectional study of 4,136 women >30 years of age with a 2-year follow-up of high-grade squamous intraepithelial lesion. Cancer Epidemiol Biomarkers Prev 2005;14:367-72.
Schweizer J, Lu PS, Mahoney CW, et al. Feasibility study of a human papillomavirus E6 oncoprotein test for diagnosis of cervical precancer and cancer. J Clin Microbiol 2010;48:4646-8.
Zhao FH, Jeronimo J, Qiao YL, et al. An evaluation of novel, lower-cost molecular screening tests for human papillomavirus in rural China. Cancer Prev Res (Phila) 2013;6:938-48.
Bouvard V, Baan R, Straif K, et al. WHO International Agency for Research on Cancer monograph working group. A review of human carcinogens--part B: biological agents. Lancet Oncol 2009;10:321-2.
Geraets DT, Heideman DA, de Koning MN, Snijders PJ, Meijer CJ, van Doorn LJ, Quint WG. High genotyping concordance between the digene HPV genotyping RH test and the reverse line blot genotyping assay on GP5+/6+-PCR products. J Clin Virol 2009;46 Suppl 3:S16-20.
Darragh TM, Colgan TJ, Thomas Cox J, et al. The lower Anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol 2013;32:76-115.
Yu LL, Kang LN, Zhao FH, et al. Elevated expression of human papillomavirus-16/18 E6 oncoprotein associates with persistence of viral infection: a 3-year prospective study in China. Cancer Epidemiol Biomarkers Prev 2016;25:1167-74.
Zhang Q, Dong L, Hu S, et al. Risk stratification and long-term risk prediction of E6 oncoprotein in a prospective screening cohort in China. Int J Cancer 2017;141:1110-9.
Doxtader EE, Brainard JA, Underwood D, et al. Knowledge of the HPV status biases cytotechnologists' interpretation of pap tests originally diagnosed as negative for intraepithelial lesion or malignancy. Cancer Cytopathol 2017;125:60-9.