The prognostic significance of HPV, p16, and p53 protein expression in vaginal cancer: A systematic review

Rasmussen, Christina Louise; Bertoli, Hanna Kristina; Sand, Freja Lærke; Kjær, Alexander K.; Thomsen, Louise T.; Kjær, Susanne K.

doi:10.1111/aogs.14260

Cited by 19 publications

(13 citation statements)

References 49 publications

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“…The prognostic significance of p53 expression in vaginal carcinoma has been investigated [ 27 , 28 , 29 , 30 , 31 , 32 ], but most did not find any. Moreover, since the reviewed cases predominantly consisted of squamous cell carcinoma rather than adenocarcinoma, the effect of TP53 mutation on the biological behavior and patient outcomes of vaginal adenocarcinoma remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Mesonephric Adenocarcinoma of the Vagina Harboring TP53 Mutation

Lee

Kim

2022

Diagnostics

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Mesonephric adenocarcinoma (MA) of the female genital tract is a rare but distinct entity, exhibiting unique morphological, immunophenotypical, and molecular characteristics. Vaginal MA is hypothesized to arise from the mesonephric remnants located in the lateral vaginal wall. A 52-year-old woman presented with vaginal bleeding. Physical examination revealed a protruding mass in the left vaginal wall. Pelvic magnetic resonance imaging revealed a 2.5-cm mass arising from the left upper vagina and extending posterolaterally to the extravaginal tissue. The punch biopsy was diagnosed as poorly differentiated adenocarcinoma. She received radical surgical resection. Histologically, the tumor displayed various architectural patterns, including compactly aggregated small tubules, solid cellular sheets, endometrioid-like glands and ducts, intraluminal micropapillae, cribriform structure, and small angulated glands accompanied by prominent desmoplastic stroma. The tubules and ducts possessed hyaline-like, densely eosinophilic intraluminal secretions. The tumor extended to the subvaginal soft tissue and had substantial perineural invasion. Immunostaining revealed positivity for the mesonephric markers, including GATA3, TTF1, and PAX2, while showing very focal and weak positivity for estrogen receptor and negativity for progesterone receptor. Additionally, we observed a complete absence of p53 immunoreactivity. Targeted sequencing analysis revealed that the tumor harbored both activating KRAS p.G12D mutation and truncating TP53 p.E286* mutation. A thorough review of the previous literature revealed that 4.5% (3/67) of vaginal/cervical MAs and 0.9% (1/112) of uterine/ovarian mesonephric-like adenocarcinomas harbor TP53 mutations, indicating that this is very uncommon in malignant mesonephric lesions. In summary, we presented a rare case of vaginal MA uniquely harboring pathogenic TP53 mutation, resulting in p53 aberration.

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Section: Discussionmentioning

confidence: 99%

Mesonephric Adenocarcinoma of the Vagina Harboring TP53 Mutation

Lee

Kim

2022

Diagnostics

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“…The early symptoms of this cancer are very subtle or lacking, so it is often diagnosed after the disease has deteriorated significantly, which makes the early diagnosis rate only 1.43%. With the development of bioinformatics, transcriptomic studies have found that some genes involved in tumorigenesis and metastasis are differentially expressed in tumor and normal tissues [72][73][74][75]. This opens the possibility for early detection of esophageal squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Common Reference Genes for Normalization of Esophageal Squamous Cell Carcinoma Gene Expression Profiles

Yang

Shao

et al. 2022

BioMed Research International

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Esophageal squamous cell carcinoma (ESCC) is one of the subtypes of esophageal cancer with Chinese characteristics, and its five-year survival rate is less than 20%. Early diagnosis is beneficial to improving the survival rate of ESCC significantly. Quantitative Real-Time Polymerase Chain Reaction is a high-throughput technique that can quantify tumor-related genes for early diagnosis. Its accuracy largely depends on the stability of the reference gene. There is no systematic scientific basis to demonstrate which reference gene expression is stable in ESCC and no consensus on the selection of internal reference. Therefore, this research used four software programs (The comparative delta-Ct method, GeNorm, NormFinder, and BestKeeper) to evaluate the expression stability of eight candidate reference genes commonly used in other tumor tissues and generated a comprehensive analysis by RefFinder. Randomly selected transcriptome sequencing analysis confirmed the SPP1 gene is closely related to ESCC. It was found that the expression trend of SPP1 obtained by RPS18 and PPIA as internal reference genes were the same as that of sequencing. The results show that RPS18 and PPIA are stable reference genes, and PPIA + RPS18 are a suitable reference gene combination. This is a reference gene report that combines transcriptome sequencing analysis and only focuses on ESCC, which makes the quantification more precise, systematic, and standardized, and promotes gene regulation research and the early diagnosis of ESCC in the future.

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“…Third, external validation on a distinct population was not carried out because a sufficiently large sample from a different population was unavailable in a single healthcare center due to VC’s extreme rareness. Finally, human papillomavirus (HPV) has been argued to be positively associated with the survival of VC patients ( 48 ). However, the HPV status of VC patients was not available in the SEER database, so it could not be controlled.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of models for predicting the overall survival and cancer-specific survival of patients with primary vaginal cancer: A population-based retrospective cohort study

Zhou

Yue

2022

Front. Med.

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BackgroundNo models have been developed to predict the survival probability for women with primary vaginal cancer (VC) due to VC’s extreme rareness. We aimed to develop and validate models to predict the overall survival (OS) and cancer-specific survival (CSS) of VC patients.MethodsA population-based multicenter retrospective cohort study was carried out using the 2004–2018 Surveillance, Epidemiology, and End Results Program database in the United States. The final multivariate Cox model was identified using the Brier score and Harrell’s C concordance statistic (C-statistic). The decision curve, calibration plot, and area under the time-dependent receiver operating characteristic curve (AUC) were used to evaluate model prediction performance. Multiple imputation followed by bootstrap was performed. Bootstrap validation covered the entire statistic procedure from model selection to baseline survival and coefficient calculation. Nomograms predicting OS and CSS were generated.ResultsOf the 2,417 eligible patients, 1,692 and 725 were randomly allocated to the training and validation cohorts. The median age (Interquartile range) was 66 (56–78) and 65 (55–76) for the two cohorts, respectively. Our models had larger net benefits in predicting the survival of VC patients than the American Joint Committee on Cancer stage, presenting great discrimination ability and excellent agreement between the expected and observed events. The performance metrics of our models were calculated in three cohorts: the training cohort, complete cases of the validation cohort, and the imputed validation cohort. For the OS model in the three cohorts, the C-statistics were 0.761, 0.752, and 0.743. The slopes of the calibration plots were 1.017, 1.005, and 0.959. The 3- and 5-year AUCs were 0.795 and 0.810, 0.768 and 0.771, and 0.770 and 0.767, respectively. For the CSS model in the three cohorts, the C-statistics were 0.775, 0.758, and 0.755. The slopes were 1.021, 0.939, and 0.977. And the 3- and 5-year AUCs were 0.797 and 0.793, 0.786 and 0.788, and 0.757 and 0.757, respectively.ConclusionWe were the first to develop and validate exemplary survival prediction models for VC patients and generate corresponding nomograms that allow for individualized survival prediction and could assist clinicians in performing risk-adapted follow-up and treatment.

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The prognostic significance of HPV, p16, and p53 protein expression in vaginal cancer: A systematic review

Cited by 19 publications

References 49 publications

Mesonephric Adenocarcinoma of the Vagina Harboring TP53 Mutation

Mesonephric Adenocarcinoma of the Vagina Harboring TP53 Mutation

Identification and Validation of Common Reference Genes for Normalization of Esophageal Squamous Cell Carcinoma Gene Expression Profiles

Development and validation of models for predicting the overall survival and cancer-specific survival of patients with primary vaginal cancer: A population-based retrospective cohort study

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