de Oliveira Neto Clariano Pires, Medeiros-Fonseca Beatriz, Estêvão Diogo, Mestre Verónica F, Costa Natália R, de Andrade Fábio Evangelista, Oliveira Paula A, Bastos Margarida M S M, Medeiros Rui, Assis Diogo, Félix Ana, Ferreira Lopes Fernanda, Gil da Costa Rui M, Brito Haissa O, Brito Luciane M O
Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranhão, São Luis 65080-805, Brazil.
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal.
Pathogens. 2021 Sep 22;10(10):1224. doi: 10.3390/pathogens10101224.
A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Portugal. Expression of estrogen receptors alpha (ERα) and beta (ERβ), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ERα and ERβ expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ERα, ERβ and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation.
越来越多的口咽鳞状细胞癌（OPSCC）与高危型人乳头瘤病毒（HPV）感染有关。出于尚不清楚的原因，HPV阳性的OPSCC在男性中比在女性中更为常见。本研究旨在确定HPV16转基因雄性和雌性小鼠中OPSCC的发病率，并探讨女性性激素受体在HPV阳性OPSCC性别易感性中的作用。2017年，在葡萄牙农业环境与生物科学研究与技术中心（CITAB），对30周龄的HPV16转基因雄性（n = 80）和雌性（n = 90）以及匹配的野生型雄性（n = 10）和雌性（n = 10）FVB/n小鼠的舌头进行组织学筛查，以检测上皮内和浸润性病变。采用免疫组织化学方法研究雌激素受体α（ERα）和β（ERβ）、孕激素受体（PR）及基质金属蛋白酶2（MMP2）的表达。使用天狼星红对胶原重塑进行研究。雌性小鼠在上皮内和浸润性病变中显示出较强的ERα和ERβ表达，同时伴有MMP2的强表达和明显的胶原重塑。雄性小鼠的ERα、ERβ和MMP2表达极少，胶原模式未改变。这些结果证实了HPV16与两性舌根癌的关联。雌性小鼠与雄性小鼠相比更高的癌症发病率与OPSCC患者的数据形成对比，并且与通过MMP2上调增强的ER表达有关。
