Diagnostic capabilities of molecular genetic parameters of HPV-infection in treatment choice of radical radiotherapy programs for early-stage cervical cancer

Cervical cancer (CC) remains one of the leading causes of female mortality. The relevance of the search for prognostic factors that allow preoperative assessment of unfavorable prognosis and avoid the need for a combined approach is beyond doubt. The prognostic significance of HPV parameters of high carcinogenic risk (HR) in relation to the course and results of СС treatment is widely discussed in the literature. At the same time, there are few studies, that highlighted relationship between traditional clinical and morphological factors with molecular genetic parameters of HPV infection and diagnostic ability of these parameters to detect unfavorable forms of the disease at the preoperative stage, and their prognostic role in the clinical outcome of early-stage CC. The results of studies are often contradicted each other, and the samples on which the studies are conducted, are heterogeneous. That justifies the relevance of the current study. The aim of the study was to investigate the relationship between clinical and morphological characteristics of CC and molecular genetic parameters of HPV infection with the assessment of diagnostic capabilities of these parameters in determining unfavorable forms of the disease and their prognostic significance with regard to the results of radical treatment of stage I CC patients. The study included 75 patients with histologically verified HPV-positive and HPV-negative stage I CC (Ia – 30/75 (40%); Ib – in 45/75 (60%)) who underwent radical specialized treatment in the form of surgery, combined treatment or combined radiation/chemoradiation therapy. The mean age of patients in the group was 43.6411.3 years. By morphologic form, squamous cell cancer prevailed in 73/75 (97.3%) cases. HPV molecular genetic parameters were determined by real-time PCR. The quantitative load of HPV DNA was expressed in logarithms of E7 genomic equivalents normalized per 100 thousand cells. In a single factor analysis, HPV mono-infection was more common in older patients (p=0.024). Viral load (VL) was lower in more advanced forms of disease (stage Ib2 compared to Ia1.2) (p=0.004), with tumor size greater than 2 cm (p=0.014) and depth of stromal tumor invasion greater than 1/3 (p=0.059). The correlation of VL before treatment with unfavorable factors, which were revealed in some patients during pathomorphological study of surgical material and were the basis for changing the stage of the disease, was analyzed. The prognostic value of VL in relation to stage change was shown: at a relatively low level of VL (lgE7/105<6.1) the probability of disease stage increase was 2.8 times higher than at a higher level of VL (lgE7/105>=6.1) (p=0.049). In multivariate analysis, no statistically significant prognostic factors for the clinical outcome of stage I CC were found (p>0.05). Molecular-genetic parameters of HPV HR can be used to assess the risk of detecting unfavorable clinical and morphological forms of stage I primary CC and to choose treatment tactics with preference of radical radiotherapy programs (combined radiotherapy/chemoradiotherapy) at low VL, in which there is a high probability of postoperative refined diagnosis with more advanced forms of disease and, accordingly, followed by adjuvant radiotherapy.