HPV mRNA tests for the detection of cervical intraepithelial neoplasia: A systematic review

Burger, Emily A.; Kornør, Hege; Klemp, Marianne; Lauvrak, V.; Kristiansen, Ivar Sønbø

doi:10.1016/j.ygyno.2010.11.013

Cited by 99 publications

(106 citation statements)

References 29 publications

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“…This side‐effect can be tackled by applying an adequate triage test for HPV‐positive women to discern those with clinically relevant disease. Various studies have evaluated triage strategies for HPV‐positive women in screening cohorts, including virus‐ and host cell‐based strategies, such as HPV16/18 genotyping,4, 5 HPV E7 mRNA analysis,6, 7 cytology,8, 9 p16/ki67 dual staining,10, 11 epigenetic changes in the host and/or viral genome,12, 13 and combinations thereof 8, 9. At present, reflex cytology testing, which has been adopted in the Dutch HPV‐based screening program, is considered an appropriate triage test,1, 4, 8, 9, 14 although a short‐term repeat cytology is needed to assure a sufficiently low risk of cervical cancer for triage test‐negative women.…”

Section: Introductionmentioning

confidence: 99%

Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up

Strooper

Berkhof

Steenbergen

et al. 2018

Intl Journal of Cancer

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DNA methylation analysis of cervical scrapes using FAM19A4 and mir124‐2 genes has shown a good clinical performance in detecting cervical cancer and advanced CIN lesions in need of treatment in HPV‐positive women. To date, longitudinal data on the cancer risk of methylation test‐negative women are lacking. In our study, we assessed the longitudinal outcome of FAM19A4/mir124‐2 methylation analysis in an HPV‐positive screening cohort with 14 years of follow‐up. Archived HPV‐positive cervical scrapes of 1,040 women (age 29–61 years), who were enrolled in the POBASCAM screening trial (ISRCTN20781131) were tested for FAM19A4/mir124‐2 methylation. By linkage with the nationwide network and registry of histo‐ and cytopathology in the Netherlands (PALGA), 35 cervical cancers were identified during 14 years of follow‐up comprising three screens (baseline, and after 5 and 10 years). The baseline scrape of 36.1% (n = 375) women tested positive for FAM19A4/mir124‐2 methylation, including 24 women with cervical cancer in follow‐up, and 30.6% (n = 318) had abnormal cytology (threshold borderline dyskaryosis or ASCUS), including 14 women with cervical cancer in follow‐up. Within screening round capability of FAM19A4/mir124‐2 methylation to detect cervical cancer was 100% (11/11, 95% CI: 71.5–100). Kaplan–Meier estimate of 14‐year cumulative cervical cancer incidence was 1.7% (95% CI: 0.66–3.0) among baseline methylation‐negative and 2.4% (95% CI: 1.4–3.6) among baseline cytology‐negative women (risk difference: 0.71% [95% CI: 0.16–1.4]). In conclusion, a negative FAM19A4/mir124‐2 methylation test provides a low cervical cancer risk in HPV‐positive women of 30 years and older. FAM19A4/mir124‐2 methylation testing merits consideration as an objective triage test in HPV‐based cervical screening programs.

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Section: Introductionmentioning

confidence: 99%

Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up

Strooper

Berkhof

Steenbergen

et al. 2018

Intl Journal of Cancer

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“…As recently highlighted in a compilation of HPV E6/E7 mRNA data, the sensitivity and specificity values obtained by different kits were quite variable (35) . Future cohort studies with larger populations and cost-benefit evaluation of screening using HPV mRNA and DNA detection and/or cytological analysis are warranted.…”

Section: Discussionmentioning

confidence: 98%

CerviCal Cytology, HPv DNa aND mrNa – a ComParative StuDy iN 162 PatieNtS

Martins¹

2012

J bras doenças sex transm

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Introduction: in contrast to the general improvement of the socioeconomic status of the Brazilian population, pathologies that are characteristic of poor health assistance persist. Among those, cervical cancer (CC) is emblematic; it still presents a persistently high incidence. Objective: to compare the performance of cervical cytology to HPV DNA and mRNA detection methods in 162 patients undergoing routine gynecological clinical practice. Methods: a total of 162 patients attended during routine gynecological examination in a private clinic in Florianópolis, Santa Catarina, Brazil, had cervical samples collected and processed for cytopathological and molecular tests, conventional PCR and NASBA. Positive samples positive for HPV DNA were submitted to Type-Specific PCR (TS-HPV PCR). Patients with altered smears were submitted to colposcopy and biopsy. Results: among the 162 samples, 19.8% (32/162) had altered smears, being 4/32 classified as ASC-H, 9/32 as ASC-US, 9/32 as LSIL and 10/32 as HSIL. Biopsies revealed nine cases of CIN I, nine CIN II and one CIN III, while seven were negative for cervical neoplasia. Overall, HPV DNA was detected in 38.3% (62/162) of the samples and HPV E6/E7 mRNA expression was found in 13.6% (22/162). Using TS-HPV PCR, HPV 16 was the most frequent type, found in 8% of the samples (5/62). Considering CIN2+ the gold-standard, cytology had 38.5% of specificity. Sensitivity and specificity of HPV-DNA PCR and NASBA were, respectively, 100% and 60%; 18.7% and 68.7%. Conclusion: mRNA E6/E7 expression was not a highly specific or sensitive marker for prevalent cervical disease while HPV DNA may be used for cervical cancer screening only in conjunction to more specific adjuvant tests.

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“…For example, the detection of specific microRNAs has shown promising results in one clinical study [109]. Furthermore, detection of the E6 protein [110,111], and E6/ E7 mRNA [66,[112][113][114] was evaluated in some clinical cohorts of hrHPV-positive women, however with disappointing results. These assays require a relatively complex genotype-specific approach and have not been shown to reach the desired NPV in hrHPV-positive women; others did not reach the required phase of marker validation and are therefore beyond the scope of this review [42,43].…”

Section: Combining Host Cell Dna Methylation Analysis With Other Markmentioning

confidence: 99%

Management of high-risk HPV-positive women for detection of cervical (pre)cancer

Luttmer

Strooper

Steenbergen

et al. 2016

Expert Review of Molecular Diagnostics

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Introduction: Primary HPV-testing has been shown to provide a superior detection of women at risk of cervical (pre)cancer compared to cytology-based screening. However, as most high-risk HPV infections are harmless, additional triage testing of HPV-positive women is necessary to identify those with cervical (pre)cancer. In this paper, we compare the performance, advantages and limitations of clinically relevant available triage strategies for HPV-positive women. Areas covered: Many different colposcopy triage strategies, comprising both microscopy-based and molecular (virus/host-related) markers, have been suggested: Pap cytology, p16/Ki-67 dual-stained cytology, HPV16/18 genotyping, viral DNA methylation and host cell DNA methylation. Literature search was limited to triage strategies that have achieved at least phase 2 of the five-phase framework for biomarker development and studies including large cohorts (≥100 hrHPV-positive women). Triage markers were stratified by sample type (cervical scrape, self-collected sample) and by study population (screening, non-attendee, referral). Expert commentary: At present, repeat Pap cytology and Pap cytology combined with HPV16/18 genotyping are the only triage strategies that have been robustly shown to be ready for implementation. Other strategies such as p16/Ki-67 dual-stained cytology and host cell DNA methylation analysis, with or without additional HPV16/18 genotyping, are attractive options for the near future. ARTICLE HISTORY

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HPV mRNA tests for the detection of cervical intraepithelial neoplasia: A systematic review

Cited by 99 publications

References 29 publications

Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up

Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up

CerviCal Cytology, HPv DNa aND mrNa – a ComParative StuDy iN 162 PatieNtS

Management of high-risk HPV-positive women for detection of cervical (pre)cancer

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