An Overview of the Mechanisms of HPV-Induced Cervical Cancer: The Role of Kinase Targets in Pathogenesis and Drug Resistance
by
, , , and
Medha Karnik
1,
SubbaRao V. Tulimilli
1
,
Preethi G. Anantharaju
1,
Anjali Devi S. Bettadapura
1,
Suma M. Natraj
1, 
Habeeb S. Mohideen
2,
Sinisa Dovat
3,
Arati Sharma
4,* and
SubbaRao V. Madhunapantula
1,5,* 1
Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory (A DST-FIST Supported Center and ICMR-Collaborating Center of Excellence), Department of Biochemistry (A DST-FIST Supported Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysore 570015, Karnataka, India
2
Bioinformatics and Integrative Omics Lab, Department of Genetic Engineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Chennai 603203, Tamil Nadu, India
3
Department of Pediatrics, Division of Hematology and Oncology, Penn State Cancer Institute, Hershey, PA 17033, USA
4
Department of Molecular and Precision Medicine, Center for Cannabis and Natural Product Pharmaceuticals (CCNPP), Penn State Cancer Institute, Hershey, PA 17033, USA
5
Special Interest Group in Cancer Biology and Cancer Stem Cells (SIG-CBCSC), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysore 570015, Karnataka, India
*
Authors to whom correspondence should be addressed.
Cancers 2026, 18(2), 318; https://doi.org/10.3390/cancers18020318
Submission received: 6 November 2025
/
Revised: 15 December 2025
/
Accepted: 8 January 2026
/
Published: 20 January 2026
(This article belongs to the Special Issue Protein Kinases and Their Impact on Tumor Growth: Mechanisms and Therapeutic Targets)
Simple Summary
Although the structure and variants of human papillomavirus (HPV) are well characterized, the mechanisms by which HPV drives cervical cancer (CC) progression and drug resistance remain poorly explored. Existing evidence suggests that high-risk HPV regulates host kinases such as Aurora kinases (A, B, C), PI3K-Akt, and GSK3α/β, which contribute to cancer cell transformation and resistance to drugs like nelfinavir and cisplatin. However, how HPV activates these kinases is still not fully understood. It also remains uncertain whether targeting these HPV-induced kinases, in combination with HPV-directed therapies such as phytopharmaceuticals or CRISPR-based systems, could improve treatment outcomes. This review explores the molecular basis of HPV-induced cervical carcinogenesis, the role of kinases in drug resistance, and the therapeutic potential of combined targeting strategies.
Abstract
Despite a thorough understanding of the structure of human papillomavirus (HPV) and its genotypic variations (high-risk and low-risk variants), the mechanisms underlying HPV-induced cervical cancer (CC) pathogenesis and the molecular signatures of drug resistance remain to be fully understood. Accumulating evidence has shown the involvement of kinase targets in the induction of drug resistance in high-risk (HR) HPV-CC. Molecularly, the genome of high-risk HPV is reported to control the expression of host kinases. In particular, Aurora kinases A, B, and C (ARKA, ARKB, and ARKC), phosphotidylinositol–trisphosphate kinase (PI3K)-Akt, and Glycogen synthase kinase3-α/β (GSK3 α/β) promote the transformation of infected cells, and also enhance the resistance of cells to various chemotherapeutic agents such as nelfinavir and cisplatin. However, the precise mechanisms through which HPV activates these kinases are yet to be fully elucidated. Furthermore, there is still ambiguity surrounding whether targeting HPV-induced kinases along with HPV-targeted therapies (such as phytopharmaceuticals and PROTAC/CRISPR-CAS-based systems) synergistically inhibit cervical tumor growth. Given the critical role of kinases in the pathogenesis and treatment of CC, a comprehensive review of current evidence is warranted. This review aims to provide key insights into the mechanisms of HPV-induced CC development, the involvement of kinases in drug resistance induction, and the rationale for combination therapies to improve clinical outcomes.
Keywords:
cervical cancer; HPV; kinases; chemoresistance
