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Oral squamous cell carcinoma (OSCC), belonging to the large and highly heterogeneous group of cancers in head and neck, corresponds to the tumors arising in the mucosal epithelium of the lips, buccal mucosa, hard palate, oral tongue (anterior 2/3 of the tongue), floor of mouth, gingiva and retromolar trigone.

口腔鳞状细胞癌（OSCC）属于头颈部大型且高度异质性的癌症组，对应于嘴唇，颊粘膜，硬腭，口腔舌（前2/3）的粘膜上皮中产生的肿瘤舌），口底，牙龈和磨牙后三角。

The most common oral sites affected by OSCC are lateral border of the oral tongue and buccal mucosa, depending on risk factors, with the first being associated mainly with cigarette smoking and the second with chewing tobacco (Miranda-Filho and Bray, 2020). Lip cancer is also highly prevalent in tropical countries (but not restricted to them) due to chronic exposure to solar radiation, but as it frequently shows a very good prognosis, studies traditionally separate it from intraoral lesions.

受OSCC影响的最常见口腔部位是口腔舌和颊粘膜的侧缘，具体取决于危险因素，第一个主要与吸烟有关，第二个与咀嚼烟草有关（Miranda-Filho和Bray，2020）。由于长期暴露于太阳辐射，唇癌在热带国家（但不限于热带国家）也非常普遍，但由于它经常显示出非常好的预后，因此传统上研究将其与口内病变分开。

Indeed, nowadays, we have enough evidence that tumors arising in the different subsites of the oral cavity show distinct and specific features and they should be studied separately (Eloranta et al., 2024).OSCC holds the poorest prognosis amongst head and neck cancers, and low survival rates remain unchanged for decades (Coletta, Yeudall and Salo, 2020).

事实上，如今，我们有足够的证据表明，口腔不同亚部位产生的肿瘤表现出不同和特定的特征，应该单独研究（Eloranta等，2024）。OSCC在头颈部癌症中预后最差，低生存率几十年来保持不变（Coletta，Yeudall和Salo，2020）。

Tumors frequently present at an advanced stage, with patients displaying locoregional disease.Although the revolutionizing targeted therapy and immunotherapy bring new perspectives for OSCC treatment, surgery in combination with radiotherapy and chemotherapy remains the primary treatment modality, which can promote chronic and lifelong morbidities with important impacts in the quality of life of patients who survive OSCC.

肿瘤经常出现在晚期，患者表现出局部区域疾病。尽管革命性的靶向治疗和免疫治疗为OSCC治疗带来了新的视角，但手术联合放疗和化疗仍然是主要的治疗方式，可以促进慢性和终身疾病，对OSCC患者的生活质量产生重要影响。

Diagnosis at an early stage (T1 or T2 with no or limited nodal disease) remains the best predictor for successful treatment..

早期诊断（T1或T2无淋巴结疾病或淋巴结疾病有限）仍然是成功治疗的最佳预测指标。。

With global incidence exceeding 389.000 new cases annually, OSCC remains one of the most common tumors worldwide, and this scenario is projected to get worse, as the incidence is estimated to rise 65% by 2050, as estimated by the Global Cancer Observatory (GLOBOCAN). Prevalence fluctuates significantly depending on the population, with crude rates ranging from 1.1 in African populations to 9.9 in populations from Oceania.

随着全球每年新发病例超过389000例，OSCC仍然是全球最常见的肿瘤之一，预计这种情况会恶化，据全球癌症观察站（GLOBOCAN）估计，到2050年，发病率估计将上升65%。患病率因人口而异，波动很大，粗发病率从非洲人口的1.1到大洋洲人口的9.9不等。

Moreover, the burden is distinct between different countries, with a clear association with human development index (HDI) and both incidence and mortality.Regarding incidence, though an increase is expected for all HDI tiers, the increase in 2050 is expected to be approximately 147.8% in low HDI countries, 94.2% in medium HDI countries, 67.3% in high HDI countries, and only 34.3% in very high HDI countries.These trends in conjunction with global disparities in therapeutic options call urgently for strategies to mitigate the growing perspective of deaths due to oral cancers in low and very low HDI countries in the coming decades..

此外，不同国家之间的负担是不同的，与人类发展指数（HDI）以及发病率和死亡率有明显的关联。关于发病率，尽管预计所有人类发展指数等级都会增加，但2050年低人类发展指数国家的增长率预计约为147.8%，中等人类发展指数国家为94.2%，高人类发展指数国家为67.3%，高人类发展指数国家仅为34.3%。这些趋势加上全球治疗选择的差异，迫切需要采取战略来缓解未来几十年人类发展指数低和非常低的国家因口腔癌死亡的日益增长的前景。。

OSCC shows a predominance in men (approximately 2.5:1), and in both male and female cases the highest incidence is reported after the fifth decade of life. However, increasing incidence in women, younger adults and people not exposed to traditional risk factors, has been consistently reported in the last two decades (for more details see Other OSCC risk factors have been suggested, including chronic oral inflammatory conditions and human papillomavirus (HPV), but the current literature remains limited, variable in quality and often underpowered.

OSCC在男性中占优势（约2.5:1），在男性和女性病例中，发病率最高的是在生命的第五个十年后。然而，在过去的二十年中，一直有报道称女性，年轻人和未接触传统危险因素的人的发病率增加（更多细节见其他OSCC危险因素，包括慢性口腔炎症和人乳头瘤病毒（HPV）），但目前的文献仍然有限，质量参差不齐，往往动力不足。

Chronic conditions promoting an oral inflammatory response such as mechanical trauma/irritation or oral dysbiosis have been described as possibly implicated in the development of OSCC, and the rationale is that multiple genetic and epigenetic changes may be induced by oxidative stress and signaling molecules related to modulation of the innate and acquired immune response (Constantin et al., 2023).

已经描述了促进口腔炎症反应的慢性病症，例如机械创伤/刺激或口腔生态失调，可能与OSCC的发展有关，其基本原理是氧化应激和与调节有关的信号分子可能诱导多种遗传和表观遗传变化。先天性和获得性免疫反应（Constantin等，2023）。

In oral dysbiotic conditions, there are also pathogen-derived genotoxins and carcinogens that may trigger oncogenic events. However, the evidence to explicitly prove that chronic oral inflammatory conditions promote and/or drive progression of OSCCs is still limited, and further detailed studies are necessary to elucidate the existing connection between these and OSCC.

在口腔益生菌条件下，也有病原体衍生的基因毒素和致癌物质可能引发致癌事件。然而，明确证明慢性口腔炎症促进和/或驱动OSCC进展的证据仍然有限，需要进一步的详细研究来阐明这些与OSCC之间的现有联系。

Although the oncogenic potential of HPV is unquestionable, particularly in oropharyngeal squamous cell carcinoma (which is closely related to OSCC), HPV studies of OSCC have largely focused on HPV-DNA detection and genotyping, with very few exploring the transcriptional activity and triggered pathways that underpin its oncogenic potential.

。

planned and standard protocols will we be able to determine the exact contribution of HPVs to OSCC occurrence..

计划和标准协议将使我们能够确定HPV对OSCC发生的确切贡献。。

Both primary and secondary prevention are top priorities for oral cancer. Historically primary prevention has focused on tobacco cessation and discontinuing heavy alcohol consumption, whereas secondary prevention is concentrated on early diagnosis or, even better, on the diagnosis and management of oral potentially malignant disorders.

一级和二级预防都是口腔癌的首要任务。从历史上看，一级预防的重点是戒烟和停止大量饮酒，而二级预防的重点是早期诊断，甚至更好的是口腔潜在恶性疾病的诊断和管理。

In 2022, the article of the IACR working group set to revise oral cancer prevention strategies confirmed the benefits of quitting tobacco use and alcohol consumption on oral cancer risk, with decreased risk with increasing time since cessation (Bouvard et al., 2022).Although the evidence was limited, the IACR working group also highlighted the benefits of cessation in the use of areca nut products, with or without tobacco.HPV vaccines were originally developed for prevention of cervical cancers, but their benefits can have broader scope, in prevention of other HPV-associated diseases, including anogenital cancers in men, oropharyngeal cancers and OSCC (Aden et al., 2024).

2022年，IACR工作组修订口腔癌预防策略的文章证实了戒烟和饮酒对口腔癌风险的益处，随着戒烟时间的延长，风险降低（Bouvard等，2022）。尽管证据有限，但IACR工作组还强调了停止使用槟榔产品（含或不含烟草）的好处。HPV疫苗最初是为预防宫颈癌而开发的，但它们的益处可能具有更广泛的范围，用于预防其他HPV相关疾病，包括男性肛门生殖器癌，口咽癌和OSCC（Aden等，2024）。

The HPV vaccines are able to prevent HPV acquisition and, to date, three types of vaccines, ranging from protection of 2 subtypes to 9 subtypes HPV, are available and recommended for both females and males (Fu et al., 2024). The importance of HPV vaccination is unquestionable for preventive medicine, but the impact on oral cancer incidence, if it occurs, is only expected to become apparent in the next decades.The diagnosis of OSCC at an early stage is still the most effective manner to reach cure, improve survival and reduce morbidity.

HPV疫苗能够预防HPV的获得，迄今为止，有三种类型的疫苗，从保护2种亚型到9种亚型HPV，可用于女性和男性（Fu et al。，2024）。HPV疫苗接种的重要性对于预防医学来说是毋庸置疑的，但如果它发生，对口腔癌发病率的影响预计只会在未来几十年内变得明显。早期诊断OSCC仍然是达到治愈，提高生存率和降低发病率的最有效方式。

In this context, oral cancer screening programs, as a strategy for early detection of oral cancer, have been developed. These programs include both general populations or individuals specifically at risk for developing an OSCC, which inclu.

在这种情况下，已经开发了口腔癌筛查计划，作为早期发现口腔癌的策略。这些计划包括普通人群或特别有发展OSCC风险的个人，其中包括。

Despite major advances and development of multiple diagnostic and therapeutic strategies, oral cancer still contributes to a large number of cancer cases and deaths around the world, and the future is alarming, as its incidence is expected to surge 65% by 2050. This trend is related to the continuous exposure to the traditional risk factors, but it may also be driven by the growing and aging of the world's population.

尽管在多种诊断和治疗策略方面取得了重大进展和发展，但口腔癌仍然在世界各地导致大量癌症病例和死亡，未来令人担忧，预计到2050年其发病率将激增65%。这种趋势与持续暴露于传统风险因素有关，但也可能是由世界人口的增长和老龄化所驱动的。

In low and very low HDI countries, where the population has limited access to an ideal healthcare system, it is more likely that the expected incidence increase will underpin more significant negative impacts. Effective educational programs for preventing tobacco and alcohol use among youth are important, and early detection is still the best way to prevent mortality and morbidity, which can be achieved through national screening programs focused on high-risk subjects.

在人类发展指数低和非常低的国家，人口获得理想医疗保健系统的机会有限，预计发病率的增加更有可能产生更大的负面影响。。

Inclusion of minimally invasive biomarkers and new AI technologies hold promise for improving diagnosis in resource-limited settings..

纳入微创生物标志物和新的人工智能技术有望在资源有限的环境中改善诊断。。