Infection with HPV starts with the access of the viral particles to basal cells in the epidermis, potentially via microtraumas to the skin. The basal cells are able to keep away these pathogens in normal circumstances through a robust immune response from the host, as HPV infections are, in general, cleared within 2 to 3 weeks. However, the rare instances of persistent infection and/or in cases where the host immune system is compromised are major risk factors for the development of lesions potentially leading to malignancy. Evolutionarily, obligatory pathogens such as HPVs would not be expected to risk exposing the host to lethal cancer, as this would entail challenging their own life cycle, but infection with these viruses is highly correlated with cancer and malignancy—as in cancer of the cervix, which is almost always associated with these viruses. Despite this key associative cause and the availability of very effective vaccines against these viruses, therapeutic interventions against HPV-induced cancers are still a challenge, indicating the need for focused translational research. In this review, we will consider the key roles that the viral proteins play in driving the host cells to carcinogenesis, mainly focusing on events orchestrated by early proteins E5, E6 and E7—the not-so-good, the bad and the ugly—and discuss and summarize the major events that lead to these viruses mechanistically corrupting cellular homeostasis, giving rise to cancer and malignancy.

中文翻译：

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不太好的、坏的和丑陋的：HPV E5、E6 和 E7 癌蛋白在致癌作用的协调中

HPV 感染始于病毒颗粒进入表皮基底细胞，可能通过皮肤微创。在正常情况下，基底细胞能够通过宿主强大的免疫反应来抵御这些病原体，因为 HPV 感染通常会在 2 至 3 周内被清除。然而，持续感染和/或宿主免疫系统受损的罕见情况是病变发展的主要危险因素，可能导致恶性肿瘤。从进化的角度来看，HPV 等强制性病原体不会让宿主面临致命癌症的风险，因为这将挑战其自身的生命周期，但这些病毒的感染与癌症和恶性肿瘤高度相关，如宫颈癌、这几乎总是与这些病毒有关。尽管有这一关键的相关原因，并且针对这些病毒有非常有效的疫苗，但针对 HPV 诱发的癌症的治疗干预措施仍然是一个挑战，这表明需要进行集中的转化研究。在这篇综述中，我们将考虑病毒蛋白在驱动宿主细胞致癌方面所起的关键作用，主要关注由早期蛋白 E5、E6 和 E7 精心策划的事件——不太好的、坏的和丑陋的——并讨论和总结导致这些病毒机械破坏细胞稳态、导致癌症和恶性肿瘤的主要事件。