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This review compiles clinical evidence on co-presence of HR-HPV and HCMV in premalignant lesions and cervical cancer, highlighting frequent detection of HCMV in HPV coinfections. 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Muñoz 2, *  \nCitation: Blanco, R.; Muñoz, J.P. HPV  \nand HCMV in Cervical Cancer: AReview of Their Co-Occurrence in Premalignant and Malignant Lesions. Viruses 2024, 16, 1699. [https://](https://)[ ](https://)[doi.org/10.3390/v16111699](doi.org/10.3390/v16111699)  \nAcademic Editor: Joe S. Mymryk  \nReceived: 25 September 2024  \nRevised: 24 October 2024  \nAccepted: 26 October 2024  \nPublished: 30 October 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Independent Researcher, Av. Vicuña Mackenna Poniente 6315, La Florida 8240000, Chile  \n2 Laboratorio de Bioquímica, Departamento de Química, Facultad de Ciencias, Universidad de Tarapacá, Arica 1000007, Chile  \n* Correspondence: [rancesblanco1976@gmail.com](rancesblanco1976@gmail.com) (R.B.); [jpmunozb@academicos.uta.cl](jpmunozb@academicos.uta.cl) (J.P.M.); Tel.: +56-582386199 (J.P.M.)  \nAbstract: Cervical cancer remains a significant global health concern, particularly in low-and middleincome countries. While persistent infection with high-risk human papillomavirus (HR-HPV) is essential for cervical cancer development, it is not sufficient on its own, suggesting the involvement of additional cofactors. The human cytomegalovirus (HCMV) is a widespread β-herpesvirus known for its ability to establish lifelong latency and reactivate under certain conditions, often contributing to chronic inflammation and immune modulation. Emerging evidence suggests that HCMV may play a role in various cancers, including cervical cancer, through its potential to influence oncogenic pathways and disrupt host immune responses. This review explores clinical evidence regarding the co-presence of HR-HPV and HCMV in premalignant lesions and cervical cancer. The literature reviewed indicates that HCMV is frequently detected in cervical lesions, particularly in those coinfected with HPV, suggesting a potential synergistic interaction that could enhance HPV’s oncogenic effects, thereby facilitating the progression from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) and invasive cancer. Although the precise molecular mechanisms were not thoroughly investigated in this review, the clinical evidence suggests the importance of considering HCMV alongside HPV in the management of cervical lesions. A better understanding of the interaction between HR-HPV and HCMV may lead to improved diagnostic, therapeutic, and preventive strategies for cervical cancer.  \nKeywords: human papillomavirus; human cytomegalovirus; co-infection; oncoproteins; cervical cancer  \n1. Introduction  \nCervical cancer is the fourth most frequently diagnosed malignant tumor and also the fourth biggest cause of cancer-related death in women worldwide [1] . In 2020, it was estimated that about 604,127 new cases of cervical cancer and 341,831 deaths were attributable to this malignancy. Cervical cancer is also the leading cause of cancer-related death in 36 countries, mainly in low-and middle-income economies [1] . Despite progress in both screening programs and treatment strategies, cervical cancer still represents an important health problem worldwide. The majority of cervical tumors (≥95%) arise from epithelial cells. Of them, 80–90% are squamous cell carcinomas (SCCs), and 9–14% areadenocarcinomas (AC), while other histological types such as adenosquamous and small cell neuroendocrine carcinomas are minorly represented (\u003C3%) [2,3] .  \nMany risk factors have been associated with cervical cancer development. These risk fac","cbCaioA206tqD0Wf","https://ap.wps.com/l/cbCaioA206tqD0Wf","pdf",997207,17,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"Why is HR-HPV necessary but not sufficient for cervical cancer development?\",\"answer\":\"HR-HPV is essential for cervical cancer development, yet it does not alone explain progression to cancer. The evidence supports the involvement of additional cofactors.\"},{\"question\":\"What role does HCMV potentially play in cervical cancer?\",\"answer\":\"HCMV is widespread and can establish lifelong latency and reactivate, contributing to chronic inflammation and immune modulation. Emerging evidence suggests it may influence oncogenic pathways and host immune responses in cervical cancer.\"},{\"question\":\"What does the reviewed literature suggest about HCMV and HPV co-occurrence?\",\"answer\":\"Clinical evidence indicates HCMV is frequently detected in cervical lesions, particularly in those coinfected with HPV, implying a potential synergistic interaction. This may enhance HPV’s oncogenic effects and facilitate progression from LSIL to HSIL and invasive cancer.\"}]","HPV and HCMV in Cervical Cancer - A Review of Their Co-Occurrence in Premalignant and Malignant Lesions | PDF",1789999560,43]