The Presence of Human Papillomavirus DNA Integration is Associated with Poor Clinical Results in Patients with Third-Stage Cervical Cancer.

The presence of virus DNA integration into the cell genome was studied for 47 primary HPV16-positive patients with morphologically verified stage III cervical cancer. By using ROC analysis, the patients were divided into two groups: with and without HPV DNA integration into the host cell genome. The differences between the groups by the histological type, degree of tumor differentiation, and primary response to therapy were statistically insignificant. Virus DNA integration more than 7-fold reduced 5-year relapse-free survival and 1.7-fold reduced overall survival rate in comparison with patients without HPV DNA integration (p=0.0002 and p=0.05, respectively). The relative risk of adverse outcome of the disease in patients with the presence of HPV16 DNA integration increases by 4 times over a period of less than 3 years (р=0.0006) at high AUC level. The probability of earlier progression of the disease in patients with of HPV DNA integration calculated according to the Cox proportional hazards model was 85.5% (hazard ratio 5.96; p=0.002). Thus, the results suggest that the presence of HPV16 DNA integration into the cell genome is an independent factor in predicting clinical outcome of advanced cervical cancer and can serve as an effective criterion for the individual choice of treatment tactics for the patients.

[The risk of neoplastic processes transformation in cervix uteri].

There was performed a comparative analysis of quantitative load and physical status of human papillomavirus (HPV) type 16 in groups of patients with cervical intraepithelial neoplasia (CIN)--25 people and cervical cancer (CC)--85 people. According to the analysis there were selected criteria appropriate to a combination of adverse factors that characterized HPV- infection and at the same time estimated both quantitative load and physical status of the virus: high viral load (> 6,5 lg copies of HPV DNA per 100000 cells) in episomal form or low load (< 6,5 lg copies of HPV DNA per 100000 cells) in integrated form of the virus. According to calculations a relative chance of appearing of CC in CIN patients with unfavorable combination of factors was 7,5 times higher than in other patients.

[The significance of physical status of human papillomavirus type 16 for predicting the effectiveness of invasive cervical cancer treatment].

For the 83 patients with HPV 16-cancer of the cervix (cervical cancer) I-III stages it was performed a comparative analysis of primary tumor response to therapy, the clinical outcome of the disease for 3-5 years after radical treatment and an evaluation of the possible contribution in these rates of the physical status of the virus. It was shown that total tumors regression in the early stages of the observation predominate in patients with "high-integrated" virus DNA (the degree of integration > 50%) of compared with a group of patients with episomal and "low-integrated" form of the virus, but in a distant periods (3-5 years) in the first group predominate an adverse outcome of disease. This pattern is true for tumors of stage I-III, and for less common--I-II stages. It is assumed that the integration of HPV16 DNA into the cellular genome may serve as an independent predictor of clinical outcome of cervical cancer.

[Infection with high-risk human papillomavirus and prognosis of cervical carcinoma].

Real-time polymerase chain reaction procedure was used to evaluate bioptic tumor samples from patients suffering cervical carcinoma (CC) stages I-IV. Out of 110 patients, high-risk human papillomavirus (HPV) infection was identified in 98 (89.1%), HPV type 16--63, HPV type 18--10 and HPV type 45--5. One of genotypes 31.33, 35, 39, 52, 58, 59 was established in 8 and a combination of several genotypes of the virus--12 patients. Frequency of remission in CC patients associated with HPV type 16 who had survived 3 years was significantly higher than in the same category associated with HPV type 18 (p=0.03). Relapse frequency and mortality rates in patients with tumors associated with one of viruses 31.33, 35, 39, 52, 58 or 59 were higher as compared with HPV type 16--associated cases 2 years (p=0.03) or 3 years on (p=0.11), respectively. A similar trend was established for squamous-cell tumors stages 1 and 2 (p=0.07) (p=0.12), respectively. No difference was observed in efficacy of therapy for infection with one or a combination of several genotypes of high-risk HPV. Hence, the genotype of virus is believed to be a factor of prognosis in CC early cancers. However, a definitive conclusion cannot be reached until results of a larger body of evidence and longer follow-up are available.

Modification of hemostatic status improves antitumor efficiency of photodynamic therapy.

Complex treatment with acetylsalicylic acid, heparin, and dexamethasone improves the efficiency of photodynamic therapy in rats with myosarcoma-I.

Effect of natural antiphospholipid antibodies on antithrombotic activity of vascular wall.

Natural latent human antibodies cross-reacting with DNA and cardiolipin, interact with human endothelial cells, decrease antiaggregation activity of rat aortic wall, and increase fibrinolytic activity of the wall of the inferior vena cava. It is assumed that natural antiphospholipid antibodies present in immunoglobulin preparations in a latent state modify antithrombogenic activity of the vascular wall and are a potential cause of antiphospholipid syndrome.