Emergency Department, National Hospital for Tropical Diseases, 78 Giai Phong, Dong Da, Hanoi, Viet Nam; Infectious Department, University of Medicine and Pharmacy, Vietnam National University, 144 Xuan Thuy, Cau Giay, Hanoi, Viet Nam.
Departments of obstetrics and gynecology, Cho Moi District General Hospital, Na Mo village, Dong Tam town, Cho Moi district, Bac Kan province, Viet Nam.
Infect Genet Evol. 2024 Jan;117:105546. doi: 10.1016/j.meegid.2023.105546. Epub 2024 Jan 3.
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.
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.
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).
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.
HPV18 参与宫颈癌的发病机制，其致癌潜能高，对不同地理区域宫颈癌分布的变化有影响，因此评估宫颈癌及其变异的特征是考虑潜在致癌 HPV18 序列变异和疫苗策略的基础。
本前瞻性研究于 2019 年 1 月 1 日至 2020 年 12 月 31 日在越南中央妇产科医院进行。采用分子诊断技术检测宫颈癌患者 HPV18 感染情况。分析 HPV18 E6、E7 和 L1 基因的核苷酸序列，以分析遗传变异。收集患者的人口统计学、临床和实验室数据并进行统计学分析。
在 48 例 HPV18 感染的宫颈癌患者中，79.2%年龄在 35-54 岁之间；而<35 岁和>54 岁的患者仅占 20.8%。所有患者在其一生中都至少怀孕过一次，其中≥3 次妊娠的患者占 83.3%。HPV18 感染引起的宫颈癌患者主要处于 0 期和 I 期，没有 II 期、III 期或 IV 期患者。单一 HPV18 感染比多重 HPV18 感染导致更多的宫颈癌病例。0 期和 I 期均出现下腹疼痛、异常绞痛性阴道排液和阴道出血等症状；然而，仅在 I 期宫颈癌患者中观察到性交后阴道出血。0 期和 I 期宫颈状态报告宫颈炎、宫颈外翻和溃疡；然而，仅在 I 期发现湿疣和溃疡。磁共振成像的结果明显优于超声。所有细胞学和病理学检查均证实为 L/HSIL、SCC、AC 和 CIS。另一方面，单一 HPV18 感染与 L/HSIL、SCC、AC 和 CIS 的风险显著高于多重 HPV18 感染。E6、E7 和 L1 基因的核苷酸序列显示 20 个突变，包括三个（E6）、五个（E7）和十二个（L1）突变。高频突变（HPV18 样本中有 95.8%-100%发生突变）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 谱系，其中 97.9%属于 AA（亚洲美洲印第安人 - A1），2.1%属于 E（欧洲 - A5）。
与同时感染 HPV18 和其他高危型的患者相比，单一 HPV18 感染的宫颈癌患者风险更高。另一方面，与 HPV18 合并感染相比，HPV18 单一感染的 L/HSIL、SCC、AC 和 CIS 发生率明显更高。在越南发现的 HPV18 株属于 A 谱系（A1 和 A5），其中包含多个致癌基因突变。
