Human Papillomavirus-Negative Cervical Cancer: A Comprehensive Review

Xing, Biyuan; Guo, Jianfeng; Sheng, Yuhan; Wu, Gang; Zhao, Yingchao

doi:10.3389/fonc.2020.606335

Cited by 66 publications

(74 citation statements)

References 70 publications

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“…Approximately 570 0 0 0 new cases and 310 0 0 0 deaths of CC are estimated annually worldwide ( Wang et al, 2019 ). Viral infections, especially human papillomavirus infection (HPV), which is recognized as one of the most common sexually transmitted infections worldwide, are now one of the known risk factors for CC ( Nishimura et al, 2021 ), i.e., CC is by far the most frequent HPV-related disease ( Xing et al, 2021 ). More than 200 genotypes of HPV have been identified so far; approximately 40 may infect genital areas ( Wang et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Genotype Distribution of Human Papillomavirus Infection among 12 076 Iranian Women

Bitarafan¹,

Hekmat²,

Khodaeian³

et al. 2021

International Journal of Infectious Diseases

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Introduction: Human papillomavirus (HPV) infection is one of the major health concerns of women in developing countries. This study gives an insight into the prevalence and genotype distribution of HPV infection and compares it with Pap smear results among Iranian women.Methods: In this study, 12 076 Iranian women underwent routine examination from November 2016 to November 2018 using HPV Direct Flow CHIP System for HPV DNA typing. Cytology was undertaken for 5138 samples.

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Section: Introductionmentioning

confidence: 99%

Prevalence and Genotype Distribution of Human Papillomavirus Infection among 12 076 Iranian Women

Bitarafan¹,

Hekmat²,

Khodaeian³

et al. 2021

International Journal of Infectious Diseases

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“…The tumor from Case #2 was an HPV-negative adenocarcinoma, and both HPV-negativity and adenocarcinoma are predictors of worse prognosis [ 18 , 19 ]. At present, it is unclear whether simultaneous mutations in KRAS and SMAD4 are enriched in HPV-negative tumors or adenocarcinoma, and collection of sufficient sample numbers to investigate this issue will be challenging because HPV-negative tumors and adenocarcinomas comprise minor subsets among cervical cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Genotypes of human papillomavirus (HPV; type 6,11,16,18,30,31,33,35,39,45,51,52,56,58,59, and 66) were determined using the PapiPlex PCR method (GeneticLab Co., Ltd., Sapporo, Japan).…”

Section: Human Papillomavirus Genotypingmentioning

confidence: 99%

Mutation Analysis of Radioresistant Early-Stage Cervical Cancer

Oike

Sekiguchi

Yoshimoto

et al. 2021

IJMS

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Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRASmt/SMAD4mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRASmt/SMAD4mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRASmt/SMAD4mt cancer cells. These data indicate that the KRASmt/SMAD4mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRASmt/SMAD4mt signature.

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“…An extensive review of HPV testing and the factors that affect false-negative results is beyond the scope of this review and has been described thoroughly in previous publications [ 35 , 36 , 37 ]. Nevertheless, these possible causes of false-negative HPV testing should be considered when diagnosing HPV-negative cervical cancers.…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathology of Human Papilloma Virus-Negative Cervical Cancers

Yoshida

Shiraishi

Kato³

2021

Cancers

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Cervical cancer is the fourth most common cancer in women worldwide and is predominantly caused by infection with human papillomavirus (HPV). However, a small subset of cervical cancers tests negative for HPV, including true HPV-independent cancers and false-negative cases. True HPV-negative cancers appear to be more prevalent in certain pathological adenocarcinoma subtypes, such as gastric- and clear-cell-type adenocarcinomas. Moreover, HPV-negative cervical cancers have proven to be a biologically distinct tumor subset that follows a different pathogenetic pathway to HPV-associated cervical cancers. HPV-negative cervical cancers are often diagnosed at an advanced stage with a poor prognosis and are expected to persist in the post-HPV vaccination era; therefore, it is important to understand HPV-negative cancers. In this review, we provide a concise overview of the molecular pathology of HPV-negative cervical cancers, with a focus on their definitions, the potential causes of false-negative HPV tests, and the histology, genetic profiles, and pathogenesis of HPV-negative cancers.

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Human Papillomavirus-Negative Cervical Cancer: A Comprehensive Review

Cited by 66 publications

References 70 publications

Prevalence and Genotype Distribution of Human Papillomavirus Infection among 12 076 Iranian Women

Prevalence and Genotype Distribution of Human Papillomavirus Infection among 12 076 Iranian Women

Mutation Analysis of Radioresistant Early-Stage Cervical Cancer

Molecular Pathology of Human Papilloma Virus-Negative Cervical Cancers

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