Prognostic Significance of HPV DNA and p16INK4a in Anal Cancer: A Systematic Review and Meta-Analysis

Urbutė, Aivara; Rasmussen, Christina Louise; Belmonte, F.; Obermueller, Theresa; Prigge, Elena-Sophie; Arbyn, Marc; Verdoodt, Freija; Kjær, Susanne K.

doi:10.1158/1055-9965.epi-19-1259

Cited by 32 publications

(19 citation statements)

References 43 publications

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“…Overexpression of the E7 protein in the transforming phase of the HPV infection increases the expression of p16 by altering its epigenetic regulation [17]. Hence, p16 is widely used as a surrogate marker for HPV infection [17,18]. In our patient cohort, p16 expression was present in 42 samples (77.8%) and absent in 11 samples (20.4%).…”

Section: Baseline Characteristicsmentioning

confidence: 76%

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Wessely

Heppt

Kammerbauer

et al. 2020

Cancers

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Anal squamous cell carcinoma (SCC) is a rare cancer with increasing incidence. Infection with high-risk human papillomavirus (HPV) subtypes is the major cause for its development. We retrospectively analyzed tumor samples from 54 anal SCC patients for infection with a panel of 32 HPV subtypes in a PCR-based approach, determined the PD-L1 expression status, and correlated the findings with the clinical data and the survival of the patients. Forty-two patients (77.8%) were HPV-positive and harbored at least one carcinogenic HPV subtype. HPV16 was the most frequently detected (n = 39, 72.2%). Four patients were infected with multiple HPV subtypes. HPV infection was significantly more often detected in female than in male patients (90.3% vs. 60.9%, p = 0.018). Patients with PD-L1 positive tumors showed a significantly better median overall survival (OS) compared with patients with PD-L1 negative tumors (69.3 vs. 28.3 months, p = 0.006). The median OS was significantly different among the distinct tumor stages (p = 0.029). Sex, grade of differentiation, and HPV infection status did not influence the median OS. Furthermore, HPV infection status and PD-L1 expression were not correlated. A multivariate Cox regression analysis revealed that PD-L1 expression status was an independent prognostic marker for survival (p = 0.012).

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Section: Baseline Characteristicsmentioning

confidence: 76%

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Wessely

Heppt

Kammerbauer

et al. 2020

Cancers

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“…The main reason is that tumor cells and normal tissues can express certain genes (23). Studies have suggested that the combined detection of imaging and molecular biology can improve the diagnosis of malignant diseases, but there is no final conclusion (24). In order to effectively avoid the above-mentioned diagnosis limitations, clinicians often advocate for the combination of multiple methods to improve the accuracy of disease diagnosis.…”

Section: A B C D Ementioning

confidence: 99%

Correlation between microvessel density (MVD) and multi-spiral CT (MSCT) perfusion parameters of esophageal cancer lesions and the diagnostic value of combined CtBP2 and P16INK4A

Dong

Feng

et al. 2021

J Gastrointest Oncol

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Background: This article aims to analyze the correlation between microvessel density (MVD) and multispiral CT(MSCT) perfusion parameters of esophageal cancer lesions, and the diagnostic value of combining C-terminal binding protein 2 (CtBP2) and P16 inhibitor of cyclin-dependent kinase 4a (P16 INK4A ). Methods: A total of 42 cases of normal esophageal mucosa tissues >5 cm from the cancer tissue were selected as the control group. The expression levels of CtBP2 and P16 INK4A and the values of MSCT perfusion parameters and MVD were compared in the control group and esophageal cancer group. SP immunohistochemical staining was used to detect protein expression levels of CtBP2 and P16 INK4A . The Pearson method was used to analyze the differences and pertinence of MSCT perfusion parameters and MVD in the control group and esophageal cancer group. The receiver operating characteristic (ROC) curve was used to calculate the diagnostic value of CtBP2 and P16 INK4A combined with MVD and MSCT perfusion parameters in esophageal cancer.Results: The positive expression rate of P16 INK4A in the esophageal cancer group was significantly lower than that in the control group. The positive expression rates of CtBP2, blood volume (BV), mean transit time (MTT), surface permeability (permeability surface, PS), and MVD values were significantly higher than those of the control group (P<0.05). There was no significant difference in blood flow (BF) value between the 2 groups (P>0.05). The BF value of the tumor invading the fibrous membrane was significantly higher than that of the non-invading fibrous membrane (P<0.05), and the PS and MVD values of the patients with lymph node metastasis were higher than those without lymph node metastasis (P<0.05). The MSCT perfusion parameters BF and BV were significantly positively correlated with MVD (P<0.05), while MTT, PS, and MVD were not significantly correlated (P>0.05). ROC results showed that the areas under curve (AUC) of CtBP2, P16 INK4A , and MSCT were 0.625, 0.747, and 0.812, respectively. However, the area under the combined detection curve was larger, at 0.869. Conclusions: MSCT perfusion imaging of esophageal cancer lesions can indirectly reflect the angiogenesis of esophageal cancer, and the combination of CtBP2 and P16 INK4A can effectively improve the diagnostic efficiency of the disease.

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“…However, studies have found that there was a certain degree of mismatch between P16 immunohistochemistry and HPV DNA detection methods [ 7 ]. Therefore, in order to gain insight into the impact of HPV and p16 on cancer, many studies have chosen to analyze HPV and P16 separately [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

The effect of HPV DNA and p16 status on the prognosis of patients with hypopharyngeal carcinoma: a meta-analysis

et al. 2022

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Objective To evaluate whether the presence of human papillomavirus (HPV) DNA and p16 might be associated with better prognosis in patients with hypopharyngeal carcinoma (HPC), especially on overall survival (OS) and disease-free survival (DFS). Method PubMed, the Cochrane Library, the Web of Science and EMBASE were searched from inception to April 2021 to search for HPV DNA- and p16-related prognostic articles on HPC. Meta-analysis was performed on the selected articles according to the inclusion and exclusion criteria. Publication bias was assessed for the included studies with Egger’s test. All studies were analyzed by using Stata 16.0 statistical software. Results A total of 18 studies were included, including 12 HPV DNA studies and 11 p16 studies. Meta-analysis showed that HPV DNA positivity was a strong prognostic factor for improved OS in patients with HPC, with a pooled hazard ratio (HR) of 0.61 (95% CI, 0.54–0.69), but there was no statistically significant difference in DFS (HR, 0.60; 95% CI, 0.31–1.16). Patients with p16-positive tumors had better OS (HR, 0.66; 95% CI, 0.49–0.89) and DFS (HR, 0.59; 95% CI, 0.44–0.78) than patients with p16-negative tumors. Conclusions This study suggests that the presence of HPV DNA leads to better OS in patients with HPC, and the presence of p16 also corresponds to better OS and DFS. Our results provide up-to-date evidence to clinicians and researchers. Larger studies adjusting for prognostic factors are needed in subsequent studies.

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Prognostic Significance of HPV DNA and p16INK4a in Anal Cancer: A Systematic Review and Meta-Analysis

Cited by 32 publications

References 43 publications

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Correlation between microvessel density (MVD) and multi-spiral CT (MSCT) perfusion parameters of esophageal cancer lesions and the diagnostic value of combined CtBP2 and P16INK4A

The effect of HPV DNA and p16 status on the prognosis of patients with hypopharyngeal carcinoma: a meta-analysis

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