背景:HPV18参与宫颈癌的发病机制,以及其高致癌潜力和对不同地理区域宫颈癌分布变异的影响,使评估宫颈癌及其变异的特征成为考虑潜在致癌HPV18序列变异和疫苗策略的基础。
方法:一项前瞻性研究于2019年1月1日至2020年12月31日在越南中央产科医院进行。使用分子诊断在宫颈癌患者中确认了HPV18感染。HPV18E6、E7和L1基因的核苷酸序列用于分析遗传变异。人口统计,临床,收集患者的实验室资料并进行统计分析。
结果:在48例感染HPV18的宫颈癌患者中,79.2%的年龄在35-54岁之间;而<35岁和>54岁的仅占20.8%。100%的患者在他们生命中的某个时候怀孕了,≥3次妊娠占83.3%。HPV18感染引起的宫颈癌患者以0期和I期为主,第二阶段没有病人,III,或者IV.单一HPV18感染比多重HPV18感染产生更多的宫颈癌病例。小腹疼痛等症状,不寻常的心绞痛放电,在0期和I期均观察到阴道出血;然而,仅在I期宫颈癌女性中发现性交后阴道出血.宫颈炎,宫颈外翻,和溃疡报告在宫颈状态阶段0和I;然而,疣和溃疡仅在I期出现。磁共振成像产生的结果远远优于超声。所有细胞学和病理检查均证实L/HSIL,SCC,AC,和CIS.另一方面,单一HPV18感染与L/HSIL的风险显著升高相关,SCC,AC,和CIS比多次HPV18感染。E6,E7和L1基因的Nulceotide序列揭示了20个突变,包括三个(E6),五(E7)和十二个(L1)突变。高频突变(95.8%-100%的HPV18样品有突变)发生在以下位置:C287G-P61P(E6基因),G5503A-R25Q,C5701G-P91R,C6460G-P344R,C6625G-P399R,和C6842G-P471R(L1基因)。基于E6/E7/L1基因序列的系统发育树显示100%属于A系,其中97.9%属于AA(亚洲美洲印第安人-A1),2.1%属于E(欧洲-A5)。
结论:单一HPV18感染的患者比同时感染HPV18和其他高危菌株的患者患宫颈癌的风险更高。HPV18单一感染,另一方面,有相当高的L/HSIL发生率,SCC,AC,和CIS比HPV18共感染。在越南发现的HPV18菌株属于谱系A(A1和A5),其中包含几个致癌基因突变。
BACKGROUND: The involvement of HPV18 in cervical cancer pathogenesis, as well as its high oncogenic potential and influence on the variation of cervical cancer distribution in different geographical regions, makes assessing the characteristics of cervical cancer and its variants the basis for considering potential carcinogenic HPV18 sequence variations and vaccine strategies.
METHODS: A prospective study was conducted at Vietnam Central Obstetrics Hospital from January 1, 2019 to December 31, 2020.
HPV18 infection was confirmed in cervical cancer patients using molecular diagnostics. Nucleotide sequences of the HPV18 E6, E7, and L1 genes were used to analyze genetic variations. The demographic, clinical, and laboratory data of the patients were collected and statistically analyzed.
RESULTS: Among 48 patients with HPV18-infected cervical cancer, 79.2% were between the ages of 35-54; while only 20.8% were < 35 and > 54 years old. 100% of patients have been pregnant at some point in their lives, with ≥3 pregnancies accounting for 83.3%. Patients with cervical cancer caused by HPV18 infection were predominantly in stages 0 and I, with no patients in stages II, III, or IV. A single
HPV18 infection generates much more cervical cancer cases than multiple
HPV18 infections. Symptoms such as lower abdomen pain, unusual anginal discharge, and vaginal bleeding were observed in both stages 0 and I; however, vaginal bleeding after sex was only detected in women with stage I cervical cancer. Cervicitis, cervical ectropion, and ulcers are reported in cervical status stages 0 and I; however, warts and ulcers were only present in stage I. Magnetic resonance imaging produces far superior outcomes than ultrasound. All cytology and pathology tests confirmed L/HSIL, SCC, AC, and CIS. On the other hand, a single HPV18 infection was associated with a significantly higher risk of L/HSIL, SCC, AC, and CIS than multiple
HPV18 infections. Nulceotide sequences of the E6, E7, and L1 genes revealed 20 mutations, including three (E6), five (E7), and twelve (L1) mutations. High-frequency mutations (95.8%-100% of HPV18 samples had mutations) occur at the following positions: C287G - P61P (E6 gene), G5503A - R25Q, C5701G - P91R, C6460G - P344R, C6625G - P399R, and C6842G - P471R (L1 gene). A phylogenetic tree based on the E6/E7/L1 gene sequence revealed that 100% belonged to A lineage, with 97.9% belonging AA (Asian Amerindian - A1) and 2.1% belonging to the E (European - A5).
CONCLUSIONS: Patients with a single HPV18 infection have a higher risk of cervical cancer than those infected with
HPV18 and other high-risk strains simultaneously. HPV18 single-infection, on the other hand, had considerably higher incidences of L/HSIL, SCC, AC, and CIS than
HPV18 co-infection. The HPV18 strain that was found in Vietnam belonged to lineage A (A1 and A5), which contains several oncogene mutations.