Characteristics of Cervical Cancer Caused by the Human Papillomavirus 18 and Its Genetic Variations in Vietnamese Women

Abstract

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).

Conclusion: 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.

Keywords: Cervical cancer; HPV18; Lineage; Multiple infections; Single infection.