Highly Effective Detection of Human Papillomavirus 16 and 18 DNA by a Testing Algorithm Combining Broad-Spectrum and Type-Specific PCR

Doorn, Leen–Jan van; Molijn, Anco; Kleter, Bernhard; Quint, Wim; Colau, Brigitte

doi:10.1128/jcm.00539-06

Cited by 152 publications

(143 citation statements)

References 41 publications

Supporting

Mentioning

136

Contrasting

Order By: Relevance

“…42 The results of studies of HPV16 variants in cervical mucosa demonstrated that non-European HPV16 variants confer a higher risk of prevalent and incident high-grade cervical dysplasia. 43 In addition, results of a case-controlled study from Mexico indicated a higher risk of invasive cervical carcinoma conferred by Asian American-North American variants (odds ratio 27.0), as compared to European HPV16 variants (odds ratio 3.4).…”

Section: Discussionmentioning

confidence: 99%

Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

2008

View full text Add to dashboard Cite

Two independent pathways of vulvar carcinogenesis have currently been identified, one related to infection with mucosal human papillomaviruses (HPVs) and a second related to chronic inflammatory or autoimmune processes. The goal of the study was to examine a possible role of cutaneous HPVs from the beta genus in vulvar carcinogenesis and to evaluate the distribution of intratypic variants of HPV 16 in HPV 16-positive vulvar cancer. Consecutive cases of vulvar carcinoma were retrieved from the files and included the following histologic subtypes: keratinizing (n ¼ 21), basaloid (n ¼ 7), warty (n ¼ 1), mixed basaloid-warty (n ¼ 4), verrucous (n ¼ 4), keratoacanthoma (n ¼ 1), basal cell carcinoma (n ¼ 1). All tumors were microdissected and tested for 25 beta HPV types and 25 mucosal HPV types. Cases identified as positive for HPV 16 were further tested for intratypic variants. All cases were immunostained for p16 INK4a . Beta HPVs were not detected in any of the tumor cases. Mucosal HPVs were detected in all but one basaloid/warty carcinomas; of these, nine cases (82%) were positive for HPV 16, including five European subtypes, one African subtype, one North American subtype and two indeterminate subtypes. Two of four verrucous carcinomas were positive for HPV 6. Mucosal HPVs were not detected in keratinizing carcinomas, keratoacanthoma and basal cell carcinoma. All cases of basaloid/warty carcinomas, but none of the remaining tumors, overexpressed p16 The pathogenesis of vulvar carcinoma is not entirely understood. Results of epidemiologic, clinicopathologic and virologic studies are in support of two independent pathways of vulvar carcinogenesis, one related to infection with oncogenic mucosal human papillomaviruses (HPVs) and a second related to a chronic inflammatory and/or autoimmune process involving vulvar mucosa and skin. [1][2][3][4][5][6] Vulvar cancers associated with oncogenic mucosal HPVs tend to occur in young women with past history of genital warts, cervical dysplasia and/or immunosuppression. These carcinomas typically belong to basaloid or warty histologic subtypes and develop from a well-characterized in situ lesion, namely, classic vulvar intraepithelial neoplasia grade 3 (VIN3).7 Approximately 80-90% of HPVpositive vulvar cancers are associated with HPV16 and nearly all remaining tumors are positive for HPV18 and HPV33. [4][5][6][8][9][10][11][12][13] Vulvar carcinomas not associated with mucosal HPVs occur in older women. These well-differentiated keratinizing squamous cell carcinomas histologically resemble conventional squamous cell carcinomas occurring in non-genital skin. 4 However, unlike the usual squamous cell carcinomas, vulvar cancers are not arising in the setting of actinic keratosis. In the vulva, these tumors develop in a background of squamous cell hyperplasia, a chronic inflammatory condition, or long-lasting lichen sclerosus, a lesion with strong links to autoimmune diseases. Although patients with lichen sclerosus

show abstract

Section: Discussionmentioning

confidence: 99%

Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

2008

View full text Add to dashboard Cite

show abstract

“…In the case of multiple infections, adding type-specific PCRs to our strategy allowed us to partially circumvent probable competition between types for primers annealing during PCR and sequencing reactions, as often observed in HPV-31 and HPV-52 infections. Recently, the combination of broad-spectrum (SPF10) and type-specific PCR has been shown to result in an even more accurate method (40).…”

Section: Discussionmentioning

confidence: 99%

“…Among these more than 40 have been shown to infect the genital tract, and 15 of them (genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) have been found to be associated with cervical cancer or high-grade cervical intraepithelial neoplasia and therefore classified as high-risk types (31). In contrast, some HPV genotypes (6,11,40,42,43, 44, 54, 61, 70, 72, 81, and CP6108) are classified as low-risk types (31). Three additional types were classified as probable high risk (26, 53, and 66) while the risk of those previously undetected remains undetermined (31).…”

mentioning

confidence: 99%

Evaluation of Combined General Primer-Mediated PCR Sequencing and Type-Specific PCR Strategies for Determination of Human Papillomavirus Genotypes in Cervical Cell Specimens

Fontaine¹,

Mascaux

Weyn³

et al. 2007

J Clin Microbiol

View full text Add to dashboard Cite

A strategy combining human papillomavirus general primer (mainly the PGMY primers)-directed PCR sequencing and type-specific PCR is presented. DNA samples were first tested in general primer-mediated PCR. The amplified fragments of positive samples after ethidium bromide-stained DNA gel analysis were further sequenced, and corresponding DNA samples were further analyzed by PCR using type-specific primers for human papillomavirus ( It is now well accepted that all cervical carcinomas contain at least one of the "high-risk" types of human papillomavirus (HPV) DNA (41). Over 100 HPV genotypes have been isolated to date. Among these more than 40 have been shown to infect the genital tract, and 15 of them (genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) have been found to be associated with cervical cancer or high-grade cervical intraepithelial neoplasia and therefore classified as high-risk types (31). In contrast, some HPV genotypes (6,11,40,42,43, 44, 54, 61, 70, 72, 81, and CP6108) are classified as low-risk types (31). Three additional types were classified as probable high risk (26, 53, and 66) while the risk of those previously undetected remains undetermined (31). Differences in geographic distribution of HPV types have been reported to exist between countries (10).Multiple concurrent and sequential infections with different oncogenic types of HPV are common, usually transient, and disappear spontaneously without clinical lesion. Only persistent high-risk HPV infection induces higher risk for the development of a high-grade precancerous lesion or cervical cancer (14,41,43). Since the absence of HPV infection means that the risk of cervical cancer is negligible, testing for HPV has now been incorporated into screening programs that previously relied only on cytology (6). HPV DNA analysis has shown encouraging results when used in conjunction with cytological analysis in primary screening for cervical cancer in women 30 years of age or older (5, 23). As a result of large randomized clinical trials, testing for HPV DNA is now recommended for most women with equivocal findings on cervical cytological analysis (atypical squamous cells of undetermined significance, also called ASCUS) (1, 28). Furthermore, HPV DNA testing provides a unique advantage for early detection of treatment failure (3,9,33,42). Recently, encouraging results with prophylactic HPV vaccines have been reported. These vaccines are believed to be effective against four different HPV types, including the most frequently encountered type, HPV-16. This further emphasizes the need for HPV DNA testing, which will be useful to guide vaccination and to monitor the frequency and the severity of infection by unaffected HPV types (15,20,21).Highly sensitive HPV DNA tests have been developed that rely on molecular biology techniques. For example, the FDA approved the HPV detection kit of Digene/Hybrid Capture 2 (HC2) manufactured by DiGene (MD). Within this test, genotype-specific RNA probes are mixed in a highrisk or a low-risk...

show abstract

“…Amplimers from the TS-PCRs were detected by DEIA similar to the method used for SPF 10 amplimer detection (16)(17)(18).…”

Section: Study Populationmentioning

confidence: 99%

Direct Comparison of HPV16 Serological Assays Used to Define HPV-Naïve Women in HPV Vaccine Trials

Safaeian

Ghosh

Porras

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

View full text Add to dashboard Cite

Background: Two HPV serological assays, the competitive Luminex immunoassay (cLIA), and an enzymelinked immunoassay (ELISA) against HPV16 have been used to define HPV-na€ ve subcohorts within large HPV vaccination trials. Some of the variation in estimated vaccine efficacies may be due to the differences in these assays used to define the HPV-na€ ve subgroups. To guide the interpretation of published results, we compared these assays.Methods: Replicate enrollment sera from a stratified sample of 388 unvaccinated women from the control arm of the Costa Rica HPV 16/18 Vaccine Trial were measured for antibodies against HPV16 using cLIA and ELISA. Agreement between the assays was estimated using standard and alternative assay cutoffs.Results: Using laboratory-determined seropositivity cutoffs, sampling-adjusted HPV16 seropositivity was 24.8% by ELISA and 7.2% by cLIA. Comparing cLIA and ELISA antibody levels based on the standard cutoffs, overall agreement was 53% (positive-agreement ¼ 49%). The poor agreement was mainly driven by the higher sensitivity of the ELISA than cLIA, resulting in 30% of the ELISA-positive sample that were cLIA-negative (none of the ELISA-negatives were cLIA-positive). Increasing ELISA cutoff to 54 ELISA units (EU)/mL (the level which maximized agreement with cLIA; ELISA standard cutoff is 8 EU/mL) resulted in higher agreement (overall agreement ¼ 91%; positive agreement ¼ 78%).Conclusions: ELISA and cLIA are different from each other based on the laboratory-determined cutoff. Increasing ELISA cutoff increased agreement with cLIA, which could facilitate comparisons among studies that use different assays.Impact: Keeping cLIA at the laboratory-determined cutoff but altering ELISA cutoff for seropositivity might facilitate vaccine efficacy comparisons in the na€ ve cohorts defined by cLIA. Cancer Epidemiol Biomarkers Prev; 21(9); 1547-54. Ó2012 AACR.

show abstract

Highly Effective Detection of Human Papillomavirus 16 and 18 DNA by a Testing Algorithm Combining Broad-Spectrum and Type-Specific PCR

Cited by 152 publications

References 41 publications

Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

Evaluation of Combined General Primer-Mediated PCR Sequencing and Type-Specific PCR Strategies for Determination of Human Papillomavirus Genotypes in Cervical Cell Specimens

Direct Comparison of HPV16 Serological Assays Used to Define HPV-Naïve Women in HPV Vaccine Trials

Contact Info

Product

Resources

About