Human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma

Huang, Chi‐Che; Lee, Li‐Ang; Tsao, Kuo‐Chien; Liao, Chun‐Ta; Yang, Lan-Yan; Kang, Chung‐Jan; Chang, Kuo‐Hsuan; Huang, Shiang‐Fu; Chen, I.-How; Yang, Shu-Li; Chen, Tse–Ching; Lin, Chien‐Yu; Fan, Kang‐Hsing; Chang, Tung-Chieh; Wang, Hung‐Ming; Yen, Tzu‐Chen

doi:10.1016/j.jcv.2014.07.007

Cited by 23 publications

(42 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, we found that HPV16 E6 increases the expression of SFMBT1 and DCUN1D1 and miR-218 rescues the function of HPV16 E6. It was observed that the presence of high-risk HPVs is associated with an increased propensity for vascular space invasion, lymph node metastasis and enlarged tumor size in some cancers [24, 25, 39]. Here, we found that HPV16 E6 promotes EMT and enhances the invasiveness of cervical cancer cells, which is consistent with the effects of SFMBT1 and DCUN1D1 and is contrary to the effect of miR-218 on cervical cancer metastasis.…”

Section: Discussionsupporting

confidence: 78%

MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer

et al. 2016

View full text Add to dashboard Cite

Repeated infection with high-risk HPV is a major cause for the development and metastasis of human cervical cancer, even though the mechanism of the metastasis is still not completely understood. Here, we reported that miR-218 (microRNA-218) was downregulated in cervical cancer tissues, especially in metastatic cancer tissues. We found that miR-218 expression was associated with clinicopathological characteristics of patients with cervical cancer. MiR-218 overexpression inhibited Epithelial-Mesenchymal Transition (EMT), migration and invasiveness of cervical cancer cells in vitro. Moreover, miR-218 repressed the expression of SFMFBT1 (Scm-like with four MBT domains 1) and DCUN1D1 (defective in cullin neddylation 1, domain containing 1) by direct binding to the 3′UTRs of the mRNAs. The overexpression of SFMBT1 induced EMT and increased the migration and invasiveness of cervical cancer cells, while the overexpression of DCUN1D1 increased the migration and invasiveness of these cells, but did not induce EMT. An inverse correlation was observed between the expression of miR-218 and DCUN1D1 protein in cervical cancer tissues. Importantly, HPV16 E6 downregulated the expression of miR-218 in cervical cancer, while miR-218 rescued the promotion effect of HPV16 E6 on the expression of SFMBT1 and DCUN1D1. Taken together, our results revealed that HPV16 E6 promoted EMT and invasion in cervical cancer via the repression of miR-218, while miR-218 inhibited EMT and invasion in cervical cancer by targeting SFMBT1 and DCUN1D1.

show abstract

Section: Discussionsupporting

confidence: 78%

MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…However, our current findings suggest that patients with HPV 16-associated OCSCC had worse 5-year LR rates following standard treatment compared to those without HPV 16 infections. Consistent with our data, recent studies show that patients with HPV-positive OCSCC had worse survival ( n : 300–1002) than those with HPV-negative OCSCC in India [39], Iran [40], Croatia [41], and Taiwan [5, 9–11, 42]. Consequently, our data should caution against the reliance on radiotherapy alone as a general treatment strategy for patients with HPV-positive OCSCC.…”

Section: Discussionsupporting

confidence: 91%

“…Patients were excluded when the following criteria were met: 1) positive surgical margins ( n = 12); 2) incomplete treatment ( n = 2); 3) loss to follow-up within 5 years ( n = 5); 4) insufficient or unusable paired pretreatment blood samples and tumor specimens ( n = 151); 5) presence of HPV infections different from HPV 16 ( n = 19); and 6) presence of multiple HPV infections ( n = 4). Two PCR assays were used to screen HPV infections: 1) a commercially available HPV L1 gene PCR assay – EasyChip HPV Blot genotyping assay (King Car Ltd.) capable of detecting 39 distinct HPV types [5, 7, 9–11, 74]; and 2) an in-house real-time PCR assay for detecting HPV 16/18 E6 and E7 oncogenes [11]. …”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was isolated with the RNeasy FFPE Kit (Qiagen) [75]. Sample handling and PCR anti-contamination strategies have been reported previously [11]. …”

Section: Methodsmentioning

confidence: 99%

“…Based on serologic methods, 28% of patients with non-oropharyngeal cancer were HPV 16 seropositive (at least one among anti-L1, anti-E1, anti-E2, anti-E4, anti- E6, and anti-E7 antibodies) [6]. Recent studies have shown that HPV 16, which constitutes a high-risk HPV type, can play multiple roles in OCSCC including tumor progression [7], lymph node metastases [8], second primary malignancies [9], distant metastases [10–11], and mortality [5, 10]. In addition, although p16 expression is not significantly associated with HPV, p16 may mediate its effects by contributing to reduced proliferative capacity, leading to smaller tumor size and lower invasive potential in OCSCC [12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular and serologic markers of HPV 16 infection are associated with local recurrence in patients with oral cavity squamous cell carcinoma

et al. 2017

Self Cite

View full text Add to dashboard Cite

Human papillomavirus (HPV) infections predict mortality in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC). To address their prognostic significance for local recurrence (LR), in this retrospective cohort study we investigated different serologic and molecular markers of HPV 16 infection in 85 consecutive patients with primary OCSCC who received standard treatment and had their sera stored before treatment. Resected tumor specimens were examined with PCR-based assays for HPV 16 E6/E7 mRNA expression. Sera were tested with suspension arrays for the presence of HPV-specific antibodies using synthetic L1 and E6 peptides as well as a synthetic E7 protein. HPV 16 E6/E7 mRNA, anti-L1, anti-E6, and anti-E7 antibodies tested positive in 12%, 25%, 38%, and 41% of the study patients, respectively. Multivariate analysis identified pathological T3/T4, E6/E7 mRNA, and anti-E7 antibodies as independent risk factors for LR, whereas anti-E6 antibodies were an independent protective factor. In patients with ≥ 3 (high-risk group), 2 (intermediate-risk), and ≤ 1 (low-risk) independent risk factors (predictors), the 5-year LR rates were 75%, 42%, and 4%, respectively. Results were validated in an independent cohort. Together, our preliminary data indicate that HPV 16 infections as well as low and high serum levels of anti-E6 and anti-E7 antibodies, respectively, can serve as biomarkers of LR in patients with OCSCC, whereas the clinical usefulness of anti-HPV 16 antibodies for risk stratification of newly diagnosed cases deserves further scrutiny.

show abstract

Association between multidisciplinary team care approach and survival rates in patients with oral cavity squamous cell carcinoma

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

Human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma

Cited by 23 publications

References 33 publications

MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer

MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer

Molecular and serologic markers of HPV 16 infection are associated with local recurrence in patients with oral cavity squamous cell carcinoma

Association between multidisciplinary team care approach and survival rates in patients with oral cavity squamous cell carcinoma

Contact Info

Product

Resources

About