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bioRxiv · 10.1101/401554

Detection of HPV16, HPV18, p16, and E6/E7 MRNA in Nasopharyngeal Cancer: A Systematic Review and Meta-Analysis

Tham, T.·Machado, R.·Khaymovich, J.·Costantino, P.
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Abstract

IntroductionHuman Papilloma Virus (HPV) associated head and neck cancers, particularly oropharyngeal cancers (OPC), have a superior prognosis to HPV negative cancers. A literature review did not find any studies that analyzed HPV 16, HPV 18 DNA and p16 in the nasopharynx subsite, although it has been reported in the oropharynx. The detection of HPV DNA and p16 in the nasopharynx could have implications for the treatment of NPC. To date no one has reported the detection or concordance rates of HPV associated markers in nasopharyngeal carcinoma (NPC).\n\nMethodsA literature search was undertaken on Medline, EMBASE, Scopus, and the Cochrane Library to identify studies that used PCR and ISH for detection of HPV DNA and p16 in the nasopharynx. We included studies published between 1992 and 2017 that reported the prognostic impact of HPV DNA and/or p16, treated HPV and p16 as categorical variables with at least 10 patients who tested for p16 and/or HPV16/HPV18 DNA in NPC, irrespective of HPV status. We then collected information from many parameters, and performed a meta-analysis to produce pooled prevalence estimates and explored sources of heterogeneity\n\nResults21 studies published between 1992 and 2017 were selected for meta-analysis, with sample sizes ranging from 10 to 1328. The total (random effects) pooled detection of any HPV marker in NPC patients was 19.7% (95% CI: 12.56 to 28.00). The total (random effects) pooled detection of p16 positivity in NPC patients was 23.98% (95% CI: 14.82 to 34.54). The total (random effects) pooled detection of HPV DNA in NPC patients, detected by ISH, was 14.43% (95% CI: 10.13 to 19.33) and for HPV DNA in NPC patients including E6/E7 was 18.13% (95% CI: 11.45 to 25.94). The total (random effects) pooled detection of HPV DNA in NPC patients was 18.13% (95% CI: 11.45 to 25.94). The total (random effects) pooled detection of EBV positivity in NPC patients was 76.21% (95% CI: 66.40 to 84.80). Heterogeneity was high for all of the results. The attributable fraction of p16+ and HPV DNA+ in NPC is 0.029. The attributable fraction of EBV positive and HPV - in NPC is 0.827. The attributable fraction of EBV negative and HPV - in NPC is 0.0639. The attributable fraction of EBV negative and HPV + in NPC is 0.085. The attributable fraction of EBV positive and HPV + in NPC is 0.023. The attributable fraction of HPV positive and mRNA+ in NPC was 0.115. The attributable fraction of p16 in NPC was 0.123.\n\nDiscussionThis is the first study that contributes to the concordance and detection rates of HPV related markers in NPC.\n\nLimitationsMost of the studies included were of Asian extraction. Most of the papers also did not test for E6/E7 RNA and therefore we are unsure of the amount of active E6/E7 RNA in NPC.

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Tham, T., Machado, R., Khaymovich, J., Costantino, P.. 2018-08-27. Detection of HPV16, HPV18, p16, and E6/E7 MRNA in Nasopharyngeal Cancer: A Systematic Review and Meta-Analysis. https://doi.org/10.1101/401554

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