Detection of circulating HPV16 DNA as a biomarker in the blood of patients with human papillomavirus‐positive oropharyngeal squamous cell carcinoma

Mazurek, Agnieszka; Rutkowski, T.; Śnietura, Mirosław; Pigłowski, Wojciech; Suwiński, Rafał; Składowski, Krzysztof

doi:10.1002/hed.25368

Cited by 19 publications

(27 citation statements)

References 41 publications

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“…These results are in contrast to our findings in which HPV16 VL was higher in nonsmokers than that in smokers. We also previously found that HPV16 VL was higher in nonsmokers in HPV-dependent oropharyngeal cancer [18].…”

Section: Discussionsupporting

confidence: 56%

“…The level of HPV16 VL observed by us in the anal cancer tissues (median 2.12; l.q 1,17 -u.q. [18]. The HPV VL of other types was slightly lower than the HPV16 VL, though, without statistical significance.…”

Section: Discussionmentioning

confidence: 85%

“…For the quantitative polymerase chain reaction (PCR), 10 μL eluate containing 50 ng DNA (measured via NanoDrop) was used. HPV was genotyped using AmpliSens® HPV HCR-genotype-titre-FRT kit (InterLabService, Moscow, Russia), which enables detection and quantification of 14 high-risk HPV (hrHPV) strains (16,18,31,33,35,39,45,51,52,56,58,59, 66, and 68). Positivity was defined as HPV Ct values below 30.…”

Section: Detection Of Hpv In the Tumor Tissuementioning

confidence: 99%

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Significance of HPV16 Viral Load Testing in Anal Cancer

Małusecka

Chmielik

Suwiński

et al. 2020

Pathol. Oncol. Res.

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Human papilloma virus (HPV) is highly frequent among patients with anal squamous cell carcinoma, but the viral load (VL) differs between patients. This study aimed to compare the rate of HPV positivity, HPV16VL, p16 INK4A and p53 expression between treatment naive and recurrent anal cancer patients. HPV was genotyped via AmpliSens® HPV HCR-genotype-titre-FRT kit. HPV16 VL was determined via quantitative polymerase chain reaction-based in-house test. p16 INK4A and p53 expression was tested via immunohistochemistry. The cohort comprised 13 treatment-naive and 17 recurrent anal SCC patients. High-risk HPV was detected in 87% of cases, and HPV16 (73%) was the predominant genotype. The rate of HPV positivity was higher among women and nonsmokers, and majority of HPV-positive cases were also p16 INK4A-positive. All p53-negative tumors were HPV16-positive. The most predominant p53 staining pattern in the HPV-positive group was scattered type, whereas it was diffuse type in the HPV-negative group. The HPV16 VL was higher in the treatment-naive group. Further, in the treatment-naive group, cases with scattered staining pattern of p53 had higher HPV16 VL than cases with diffuse staining pattern. The opposite result was noted in the recurrent cancer group. Moreover, p16-positive cases with scattered p53 staining pattern in the treatment naive group had higher HPV16 VL than their counterparts in the recurrent cancer group. In conclusion, the HPV VL, as is the association between VL and p16 INK4A /p53, is in an inversed trend in treatment naive and recurrent cancer patients, highlighting the importance of HPV VL measurement in anal SCC.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 85%

Section: Detection Of Hpv In the Tumor Tissuementioning

confidence: 99%

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Significance of HPV16 Viral Load Testing in Anal Cancer

Małusecka

Chmielik

Suwiński

et al. 2020

Pathol. Oncol. Res.

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“…In other words, EBV DNA in patients with NPC has a tendency to be specific for men with N2/N3 disease who never smoked. Interestingly, a similar tendency was also observed in HPV‐positive patients oropharyngeal cancer in our previous study . We showed that in patients with oropharyngeal cancers, no smoking and advanced N disease were the most important predictors for circulating HPV16 DNA in the blood.…”

Section: Discussionsupporting

confidence: 87%

Prognostic significance of Epstein‐Barr virus viral load in patients with T1‐T2 nasopharyngeal cancer

Mazurek

Wygoda

Rutkowski

et al. 2019

Journal of Medical Virology

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Nasopharyngeal cancer (NPC) is highly prevalent in southern Chinese populations but it is rare in most parts of the world. A few studies were performed in nonendemic regions of the world, and suggested the prognostic value of Epstein-Barr virus (EBV) DNA load in blood. In this study, EBV DNA presence and viral load (VL) level in the blood of patients with NPC in Polish population were presented. In addition, its prognostic value for locoregional control among other clinicopathological features was evaluated. Patients with carcinoma of the nasopharynx treated definitively with radiotherapy or radiochemotherapy were included in the study. Real-time polymerase chain reaction was performed for quantitating of EBV DNA in plasma. Among patients with NPC, 51% (22 of 43) were classified as EBV-positive with the mean of the VL of 4934 ± 8693 copies/mL. Multiple regression analysis between log EBV DNA VL and clinical parameters revealed that the most important factors increasing the VLs were advanced N disease together with no-smoking status and advanced T tumors. Multivariate Cox regression analysis revealed that T3-T4 tumors were an independent prognostic factor for poor locoregional control. Analysis for the subgroup of patients with T1-T2 tumors showed that T1-T2 EBV-negative patients had better locoregional control compared with T1-T2 EBV-positive, though without statistical significance. In conclusion, it seems that EBV DNA determination may have an important role in diagnostics of patients with NPC with T1-T2 tumors indicating a subgroup with poorer prognosis, though it needs to be proven on a larger cohort. K E Y W O R D SEpstein-Barr virus, locoregional control, nasopharyngeal cancer, plasma, viral load

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“…Plasma circulating tumour HPV DNA (ctHPVDNA) is a promising biomarker for monitoring treatment responses in patients with HPV-associated OPC [15]. According to the results, the patients with ctHPVDNA OPC possessed significantly higher HPV DNA viral loads in their tumour tissues than the ctHPVDNA-negative patients [16]. Longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence [17].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel methylation markers in HPV-associated oropharyngeal cancer: genome-wide discovery, tissue verification and validation testing in ctDNA

et al. 2020

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Human papilloma virus (HPV)-associated oropharyngeal cancer (OPC) is an independent tumour type with regard to cellular, biological, and clinical features. The use of non-invasive biomarkers such as circulating tumour DNA (ctDNA) may be relevant in early diagnosis and eventually improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC). Genome-wide discovery using RNA sequencing and reduced representation bisulfite sequencing yielded 21 candidates for methylation-targeted genes. A verification study (252 HNSCC patients) using quantitative methylationspecific PCR (Q-MSP) identified 10 genes (ATP2A1, CALML5, DNAJC5G, GNMT, GPT, LY6D, LYNX1, MAL, MGC16275, and MRGPRF) that showed a significant increase recurrence in methylation groups with OPC. Further study on ctDNA using Q-MSP in HPV-associated OPC showed that three genes (CALML5, DNAJC5G, and LY6D) had a high predictive ability as emerging biomarkers for a validation set, each capable of discriminating between the plasma of the patients from healthy individuals. Among the 42 ctDNA samples, methylated CALML5, DNAJC5G, and LY6D were observed in 31 (73.8%), 19 (45.2%), and 19 (45.2%) samples, respectively. Among pre-treatment ctDNA samples, methylated CALML5, DNAJC5G, and LY6D were observed in 8/8 (100%), 7/8 (87.5%), and 7/8 (87.5%) samples, respectively. Methylated CALML5, DNAJC5G, and LY6D were found in 2/8 (25.0%), 0/8 (0%), and 1/8 (12.5%) of the final samples in the series, respectively. Here, we present the relationship between the methylation status of three specific genes and cancer recurrence for risk classification of HPV-associated OPC cases. In conclusion, ctDNA analysis has the potential to aid in determining patient prognosis and real-time surveillance for disease recurrences and serves as an alternative method of screening for HPVassociated OPC.

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Detection of circulating HPV16 DNA as a biomarker in the blood of patients with human papillomavirus‐positive oropharyngeal squamous cell carcinoma

Cited by 19 publications

References 41 publications

Significance of HPV16 Viral Load Testing in Anal Cancer

Significance of HPV16 Viral Load Testing in Anal Cancer

Prognostic significance of Epstein‐Barr virus viral load in patients with T1‐T2 nasopharyngeal cancer

Identification of novel methylation markers in HPV-associated oropharyngeal cancer: genome-wide discovery, tissue verification and validation testing in ctDNA

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