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Untold story of human cervical cancers: HPV-negative cervical cancer

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Cervical cancer is the fourth most common malignancy in womenworldwide. Although infection from human papillomavirus (HPV)has been the leading cause of cervical cancer, HPV-negativecervical cancer accounts for approximately 3-8% of all cases. Previous research studies on cervical cancer have focused onHPV-positive cervical cancer due to its prevalence, resulting inHPV-negative cervical cancer receiving considerably less attention. As a result, HPV-negative cervical cancer is poorly understood. Its etiology remains elusive mainly due to limitations inresearch methodology such as lack of defined markers and modelsystems. Moreover, false HPV negativity can arise from inaccuratediagnostic methods, which also hinders the progress of researchon HPV-negative cervical cancer. Since HPV-negativecervical cancer is associated with worse clinical features, greaterattention is required to understand HPV-negative carcinoma. Inthis review, we provide a summary of knowledge gaps andcurrent limitations of HPV-negative cervical cancer research basedon current clinical statistics. We also discuss future directionsfor understanding the pathogenesis of HPV-independent cervicalcancer. [

Abstract

Cervical cancer is the fourth most common malignancy in womenworldwide. Although infection from human papillomavirus (HPV)has been the leading cause of cervical cancer, HPV-negativecervical cancer accounts for approximately 3-8% of all cases. Previous research studies on cervical cancer have focused onHPV-positive cervical cancer due to its prevalence, resulting inHPV-negative cervical cancer receiving considerably less attention. As a result, HPV-negative cervical cancer is poorly understood. Its etiology remains elusive mainly due to limitations inresearch methodology such as lack of defined markers and modelsystems. Moreover, false HPV negativity can arise from inaccuratediagnostic methods, which also hinders the progress of researchon HPV-negative cervical cancer. Since HPV-negativecervical cancer is associated with worse clinical features, greaterattention is required to understand HPV-negative carcinoma. Inthis review, we provide a summary of knowledge gaps andcurrent limitations of HPV-negative cervical cancer research basedon current clinical statistics. We also discuss future directionsfor understanding the pathogenesis of HPV-independent cervicalcancer. [

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