A Systematic Review and Meta-Analysis of Prognostic Biomarkers in Anal Squamous Cell Carcinoma Treated With Primary Chemoradiotherapy

Parwaiz, Iram; Maccabe, Tom A; Thomas, Michael G.; Messenger, David E.

doi:10.1016/j.clon.2019.06.013

Cited by 20 publications

(26 citation statements)

References 47 publications

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“…Another remarkable finding of this study was the positivity of p16 INK4a in more than half of HPV positive cases and in comparison with its negativity in HPV-negatives, showing its high specificity and strong association with the carcinogenesis mediated by the inhibition of p53 and pRb tumor suppressor proteins. Our results confirmed that p16 INK4a over expression could be adopted as an immuno-histochemical prognostic marker, as reported in head and neck HPV-associated cancers [34,35].…”

Section: Discussionsupporting

confidence: 90%

Distribution of HPV Genotypes in Patients with a Diagnosis of Anal Cancer in an Italian Region

Muresu

Sotgiu

Saderi

et al. 2020

IJERPH

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Objectives: Anal cancer is a rare disease. However, its incidence is increasing in some population groups. Infection caused by Human Papillomavirus (HPV) is strongly associated with the risk of anal cancer, whose variability depends on samples, histology, and HPV detection methods. The aim of the study was to assess prevalence and distribution of HPV genotypes in patients diagnosed with anal carcinoma. Methods: An observational, retrospective study was carried out in a tertiary care hospital in North Sardinia, Italy. Specimens of anal cancer diagnosed from 2002–2018 were selected. Demographic, epidemiological, and clinical variables were collected to assess their relationship with the occurrence of anal cancer. Results: The overall HPV positivity was 70.0% (21/30), with HPV-16 being the predominant genotype (~85%). The highest prevalence of anal cancer was in patients aged ≥55 years. HPV positivity was higher in women (p-value > 0.05) and in moderately differentiated samples (G2) (p-value < 0.05). p16INK4a and E6-transcript positivity were found in 57% and 24% of the HPV positive samples, respectively. The OS (overall survival) showed a not statistically significant difference in prognosis between HPV positive sand negatives (10, 47.6%, vs. 4, 44.4%; p-value = 0.25). Conclusions: HPV-DNA and p16INK4a positivity confirmed the role of HPV in anal carcinoma. Our findings could support the implementation and scale-up of HPV vaccination in males and females to decrease the incidence of HPV-associated cancers. Further studies are needed to better clarify the prognostic role of HPV/p16 status.

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Section: Discussionsupporting

confidence: 90%

Distribution of HPV Genotypes in Patients with a Diagnosis of Anal Cancer in an Italian Region

Muresu

Sotgiu

Saderi

et al. 2020

IJERPH

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“…The role of HPV infection as a prognostic factor associated with better response to CRT treatment or survival was not confirmed in our ASCC cohort as was reported by other studies [ 13 , 15 ]. This could be associated with the reduce number of ASCC patients without HPV infection (13%) detected in our cohort.…”

Section: Resultscontrasting

confidence: 42%

“…The relapse pattern is mostly locoregional, while distant metastases are seen in approximately 10% of ASCC cases [12] . Clinical prognostic factors associated with poor ASCC outcomes include gender, tumor stage, and incomplete radiotherapy doses [13] . In addition to high-risk HPV infections, TP53 wild-type status and p16 protein overexpression have been proposed as predictive biomarkers of a better response to standard therapy in oropharyngeal and anogenital SCC [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to high-risk HPV infections, TP53 wild-type status and p16 protein overexpression have been proposed as predictive biomarkers of a better response to standard therapy in oropharyngeal and anogenital SCC [ 14 , 15 ]. Nevertheless, not all HPV-positive patients achieve a CR, and local recurrence is reported in approximately 25% of ASCC cases [13] . In other words, we still have no understanding on why only some ASCC respond to CRT whereas others appear not to do requiring an abdominiperineal resection.…”

Section: Introductionmentioning

confidence: 99%

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A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma

Iseas¹,

Golubicki²,

Robbio³

et al. 2021

Translational Oncology

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Highlights High-risk HPV infection is less frequently detected in HIV-positive non-metastatic ASCC compared with HIV-negative cases. Mutational profile identified in the non-metastatic ASCC cohort revealed expected similarities with metastatic ASCC. High PD-L1 expression levels are associated with high CD3 and CD8 TIL density, complete response to treatment, and good survival outcome of ASCC patients. PD-L1 is a reliable predictive and prognostic biomarker that allows the stratification in low- vs. high-risk ASCC patients at their initial therapeutic approach.

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“…Two reviews and meta-analyses of the role of HPV DNA in anal cancer survival have previously been published (14,15). In this metaanalysis of overall survival (OS) according to HPV DNA status we included three times more cases of anal cancer (>1,700).…”

Section: Introductionmentioning

confidence: 99%

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

Urbutė

Rasmussen

Belmonte

et al. 2020

Cancer Epidemiology, Biomarkers &Amp; Prevention

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We conducted a systematic review and meta-analysis of observational studies evaluating survival in patients with anal cancer, according to human papillomavirus (HPV) DNA, p16 INK4a , and combined HPV DNA/p16 INK4a status. We systematically searched PubMed, EMBASE, and Cochrane Library databases to identify studies published in English until July 25, 2018, directly providing or allowing estimation of survival of patients with anal cancer according to the presence of HPV DNA and/or overexpression of p16 INK4a . We estimated pooled HRs and 95% confidence intervals (CI) for overall survival (OS) using a random-effects model. We included 16 studies, comprising 1,724 patients with anal cancer tested for HPV DNA (65% positive), and 567 patients tested for p16 INK4a (87% positive). The pooled HR for OS was 0.54 (95% CI, 0.33-0.89) for HPV DNA positive versus negative, 0.37 (95% CI, 0.24-0.57) for p16 INK4a positive versus negative, and 0.36 (95% CI, 0.22-0.58) for HPV DNA positive/p16 INK4a positive versus HPV DNA positive/p16 INK4a negative patients with anal cancer. Patients with HPV DNA or p16 INK4a positive anal cancer have significantly better OS compared with HPV DNA or p16 INK4a negative. This points to the possible value of HPV DNA and/or p16 INK4a testing when planning the management and follow-up strategy for patients diagnosed with anal cancer. Data extractionTwo authors (A. Urbute and C.L. Rasmussen) reviewed titles, abstracts, and full-texts, and extracted data independently. Any inconsistency in the evaluation of study eligibility or data extraction was

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A Systematic Review and Meta-Analysis of Prognostic Biomarkers in Anal Squamous Cell Carcinoma Treated With Primary Chemoradiotherapy

Cited by 20 publications

References 47 publications

Distribution of HPV Genotypes in Patients with a Diagnosis of Anal Cancer in an Italian Region

Distribution of HPV Genotypes in Patients with a Diagnosis of Anal Cancer in an Italian Region

A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma

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

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