Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types

Menzo, Stefano; Ciavattini, Andrea; Bagnarelli, Patrizia; Marinelli, Katia; Sisti, S.; Clementi, Massimo

doi:10.1186/1471-2180-8-112

Cited by 26 publications

(22 citation statements)

References 12 publications

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“…izations occurred with types HPV-53, HPV-66, and HPV-70, which are phylogenetically related to the HPV types included in HC2 (34,35), which is consistent with observations in previous studies (10-13, 16, 20). Increasing age (as was also observed in the ARTISTIC study [20]), the use of the PreservCyt transport medium, and a low RLU/PC ratio were significantly associated with false-positive HC2 results.…”

Section: Discussionsupporting

confidence: 92%

Clinical Impact of the Analytical Specificity of the Hybrid Capture 2 Test: Data from the New Technologies for Cervical Cancer (NTCC) Study

et al. 2013

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The Hybrid Capture 2 (HC2) test targets 13 human papillomavirus (HPV) types. Here, cross-reactivity with non-HC2-targeted HPV types is described. We aimed to define the proportion of HC2-positive women who had negative results with HC2-targeted HPV types and estimate its determinants and impact on women's health management. The New Technologies for Cervical Cancer (NTCC) trial was followed in two predetermined phases. Women in the experimental arm were tested for the presence of HPV DNA by HC2 following a sample collection in PreservCyt (first phase) or Digene specimen transport medium (STM) (second phase). HPV genotyping was performed on DNA samples from HC2-positive women by PCR with GP5 ؉ /GP6 ؉ primers and reverse line blot (RLB) hybridization. Untyped samples were submitted to direct sequencing or restriction fragment length polymorphism. Multivariate logistic regression analysis estimated the adjusted odds ratios ( C ervical screening has the main purpose of decreasing the burden of cervical cancer by detecting and treating highgrade cervical intraepithelial neoplasia (CIN). Highly sensitive and specific tests have been established to identify the human papillomavirus (HPV) infections that are associated with detectable CIN. Double-testing studies (1) and randomized controlled trials (RCTs) (2-6) have highlighted Hybrid Capture 2 (HC2) as a highly sensitive test (Ͼ95%) (7) for detecting highgrade CIN. Conversely, the HC2 test showed lower clinical specificity than did cytology (90%) (7). Most of the false positives that make the test specificity so low are due to women who are actually infected by a high-risk HPV type but who have not developed high-grade lesions and, in most cases, will never develop cervical lesions (8). To date, this drawback has been overcome by the introduction of triage procedures that limit the referrals of HPV-positive women for unnecessary diagnostic procedures.It has been claimed that HC2 also has analytical false-positive results. HC2 includes a cocktail of probes designed to detect 13 HPV types, which are classified by the International Agency for Research on Cancer (IARC) (9) as carcinogenic with sufficient evidence (group 1), and HPV-68, which is classified as probably carcinogenic (group 2A). Some studies have shown cross-reactivity with other HPV types that are phylogenetically related to the targeted genotypes (10)(11)(12)(13)(14)(15)(16)(17)(18)(19).Increasing analytical false positives were observed with decreasing viral load, as measured by the ratio between the relative light units (RLU) of the specimen and the RLU of a positive cutoff (PC) consisting of 1 pg/ml of HPV DNA (RLU/PC ratio) (11,15,(20)(21)(22). In addition, lower reproducibility of the HC2 results between laboratories (23) and lower agreement between HC2 and PCR with the MY09 to MY11 primers when followed by dot blot hybridization (19) was reported with samples collected in PreservCyt (which is used for liquid-based cytology) than in those collected in the Digene standard transport medium (STM); this su...

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Section: Discussionsupporting

confidence: 92%

Clinical Impact of the Analytical Specificity of the Hybrid Capture 2 Test: Data from the New Technologies for Cervical Cancer (NTCC) Study

et al. 2013

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“…However, besides their highly variable geographic distribution and frequency, some of these types still do not have a defined pathogenic potential. In a work involving approximately 2,000 samples, 36% of unclear identifiable HPV infections were verified 23 . The clinical effects of these viruses cannot be determined according to their biological properties.…”

Section: Discussion Rev Soc Bras Med Trop 43(1):4-8 Jan-fev 2010mentioning

confidence: 99%

Human papillomavirus genotypes in asymptomatic young women from public schools in Rio de Janeiro, Brazil

Oliveira

Ferreira

Augusto

et al. 2010

Rev. Soc. Bras. Med. Trop.

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INTRODUCTION: The aim of this work was to survey HPV information from a random population of young women from Rio de Janeiro, Brazil. METHODS: This cross-sectional study included cervical samples from 241 female students. To determine human papillomavirus status, polymerase chain reaction amplification was performed. HPV typing was determined by restriction fragment length polymorphism analysis. Demographic data, life style, sexual and gynecological history were obtained through use of a structured questionnaire. RESULTS: The average age of the women was 19.6 years-old (SD=3.4 years). HPV prevalence was 27.4%. Nineteen different HPV genotypes were detected, including 13 high risk types. HPV 16 was the most prevalent type (6.2%), followed by 31 (4.1 %) and 66 (3.7%). Most of the oncogenic types belonged to the A9 species (28/48). The frequency of women infected by at least one oncogenic type was significantly higher than those only infected by low risk types (18.7% versus 7.5%). Cervical changes were detected in 12.5% of the sample and were significantly linked to infection with HPV types of the A9 species. Demographic variables, sexual initiation, or number of sexual partners were not associated with HPV prevalence, variety of HPV genotypes or oncogenic types. CONCLUSIONS: The relative frequency of HPV genotypes other than vaccine types in young females should be taken into account when evaluating vaccination strategies. Due to the high prevalence of HPV infection among the population studied, implementation of sex education in schools, promotion of condom use and an organized screening program to prevent cervical cancer must be encouraged for this age group.

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“…Most are cleared without consequences while some proportion can persist in severe lesions and eventually progress to cervical dysplasia and invasive malignancies (Menzo et al, 2008). The persistence of HPV infection is associated with high-risk HPV types and encountered more frequently in women above the age of 30 (Forslund et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Clinical Prediction Based on HPV DNA Testing by Hybrid Capture 2 (HC2) in Combination with Liquid-based Cytology (LBC)

Junyangdikul

Tanchotsrinon²,

Chansaenroj³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Primary screening by HPV DNA testing is an effective method for reducing cervical cancer and has proven more sensitive than cytology. To advance this approach, many molecular methods have been developed. Hybrid capture 2 provides semi-quantitative results in ratios of relative light units and positive cutoff values (RLU/ PC). Twenty-five thousand and five patients were included in this study to analyze the correlation between the ratio of RLU/PC and stage of cervical dysplasia. The results show that the RLU/PC ratios ranged from 0-3500 while almost normal cases, ASC-US and ASC-H, had values below 200. Of those samples negative for cytology markers, 94.6% were normal and their RLU/PC ratios were less than 4. With an RLU/PC ratio greater than 4 and less than or equal to 300, the percentages in all age groups were normal 53.6%, LSIL 20.2%, ASC-US 17.2%, HSIL 6.13%, ASC-H 2.72%, and AGC 0.11%, respectively. In contrast, 64.0% of samples with a RLU/ PC ratio greater than 300 and less than or equal to 3500 were LSIL. These results should contribute to cost effective cervical cancer management strategies. Further studies of associations with particular HPV genotypes would be useful to predict the risk of progression to cancer.

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Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types

Cited by 26 publications

References 12 publications

Clinical Impact of the Analytical Specificity of the Hybrid Capture 2 Test: Data from the New Technologies for Cervical Cancer (NTCC) Study

Clinical Impact of the Analytical Specificity of the Hybrid Capture 2 Test: Data from the New Technologies for Cervical Cancer (NTCC) Study

Human papillomavirus genotypes in asymptomatic young women from public schools in Rio de Janeiro, Brazil

Clinical Prediction Based on HPV DNA Testing by Hybrid Capture 2 (HC2) in Combination with Liquid-based Cytology (LBC)

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