HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer

Abstract

This study is aimed at searching for an informative predictor of the clinical outcome of cervical cancer (CC) patients. The study included 135 patients with locally advanced cervical cancer (FIGO stage II-III) associated with human papillomavirus (HPV) 16/18 types or negative status of HPV infection. Using logistic regression, we analyzed the influence of the treatment method, clinical and morphological characteristics, and the molecular genetic parameters of HPV on the disease free survival (DFS) of patients treated with radiotherapy or chemoradiotherapy. Multivariate analysis revealed three factors that have prognostic significance for DFS, i.e., HPV-related biomarker (HPV-negativity or HPV DNA integration into the cell genome) (OR = 9.67, p = 1.2 × 10^-4), stage of the disease (OR = 4.69, p = 0.001) and age (OR = 0.61, p = 0.025). The predictive model has a high statistical significance (p = 5.0 × 10^-8; Nagelkirk's R² = 0.336), as well as sensitivity (Se = 0.74) and specificity (Sp = 0.75). Thus, simultaneous accounting for the clinical and molecular genetic predictors (stage of the disease, patient age and HPV-related biomarker) makes it possible to effectively differentiate patients with prognostically favorable and unfavorable outcome of the disease.

Keywords: cervical cancer; chemoradiotherapy; human papillomavirus; prognosis; radiotherapy.

Figure 1

Distribution of 135 patients with cervical cancer (CC) by the treatment methods: radiation therapy (RT), concurrent chemoradiation therapy (CCRT) or neoadjuvant chemotherapy followed by radiotherapy (NACT + RT).

Figure 2

Correlation of molecular genetic parameters of human papillomavirus (HPV)16/18 (n = 115). Y-axis: 0%—no integration of HPV DNA into the host cell genome (episomal form), 100%—complete integration.

Figure 3

ROC-curve, built on the basis of data on the degree of integration of HPV 16/18 DNA into the cell genome (from 0% in the absence of integration to 100% in the case of complete integration), to select optimal discriminator that separates patients into groups with relatively favorable and unfavorable clinical outcome of the disease.

Figure 4

Disease free survival of CC patients with stages II (a) and III (b) depending on the physical state of the viral genome (episomal or integrated form).

Figure 5

Disease free survival of CC patients with stages II (a) and III (b) depending on the absence/presence of the biomarker (HPV-negativity or integration of HPV16/18 DNA into the cell genome).