Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer

Abstract

To obtain information on the incidence and the clinical significance of infection with various types of the human papillomavirus (HPV) in cancer of the uterine cervix, we retrospectively examined the HPV status of 106 patients who had received radical radiotherapy for cervical cancer stages IB to IIIB. DNA was extracted from formalin-fixed, paraffinembedded biopsies and PCR was carried out to identify HPV types 16, 18, 31, 35, 33 and 45. To detect additional HPV types, consensus PCR products were cloned and sequenced. A catalyzed signal-amplified colorimetric in situ hybridization was carried out in 84 of 106 specimens as a positive control. Response to therapy, progression-free survival (PFS) and cervical cancer-specific survival (CCSS) were the statistical endpoints. Survival analysis was carried out using univariate and multivariate analysis (Cox regression). Ninety-six patients (90.6%) were HPV-positive and 42/96 (43.7%) were positive for multiple HPV types. Eight patients had persistent disease after radiotherapy. From these 8 patients, 7 were infected with multiple HPV types and only 1 patient had an infection with a single HPV type. After a median follow up period of 50 months, patients with multiple HPV infection had a significantly shorter PFS and CCSS compared to those with single HPV infection (24.8% and 34.9% vs. 64% and 60.8%, Log rank, p < 0.01 and 0.04). In multivariate analysis, the presence of multiple HPV types (RR 1.9), node status (RR 2.3), tumor size (RR 3.2) and histologic type (RR 4.8) were independent prognostic factors of CCSS. Our results demonstrate that the presence of multiple HPV types is associated with poor response and with reduced survival in cervical cancer patients who receive radiotherapy as the primary treatment.

Expression of growth-regulated oncogene-1, hepatocyte growth factor, platelet-derived growth factor-AA and soluble E-selectin and their association with high-risk human papillomavirus infection in squamous cell carcinoma of the uterine cervix

“…However, no significance was found between HPV infection and clinicopathological variables, which is consistent with the study by Bachtiary et al (36). The association between HPV and the four biomarkers was also analyzed and only the serum levels of HGF in HPV-positive patients were higher than HPV-negative patients.…”

Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development

“…Выявленная одними авторами корреляция содержания HIF-1a со стадией заболевания не подтверждается работами других авторов [24,69,72,73]. Некоторыми авторами также сообщается об отсутствии достоверной взаимосвязи HIF-1a с размером опухоли и статусом лимфоузлов [69][70][71][72][73], что не позволяет однозначно судить о роли HIF-1a в метастазировании РШМ.…”

“…Выявленная одними авторами корреляция содержания HIF-1a со стадией заболевания не подтверждается работами других авторов [24,69,72,73]. Некоторыми авторами также сообщается об отсутствии достоверной взаимосвязи HIF-1a с размером опухоли и статусом лимфоузлов [69][70][71][72][73], что не позволяет однозначно судить о роли HIF-1a в метастазировании РШМ. В то же время, многие исследователи отмечают сильную отрицательную корреляцию уровня экспрессии HIF-1a с общей/безрецидивной выживаемостью больных РШМ, ответом на первичную радиотерапию и вероятностью рецидива, на основании чего предлагается рассматривать HIF-1a как независимый прогностический фактор [70,[74][75][76].…”

Impact of human papillomavirus genotype on response to treatment and survival in patients receiving radiotherapy for squamous cell carcinoma of the cervix

“…Previous attempts to determine the prognostic significance of the presence or absence of detectable HPV dna and hpV types in cervical cancer patients have generated conflicting results (6)(7)(8)(9)(10)(11)(12)(13). Some studies have reported that patients infected with HPV-18 had worse prognoses and higher disease recurrence rates than patients with hpV-16 infection (6)(7)(8)10). In a recent study, infection with multiple hpV types was also considered an indicator of poor response to radiotherapy (7,11).…”

“…Some studies have reported that patients infected with HPV-18 had worse prognoses and higher disease recurrence rates than patients with hpV-16 infection (6)(7)(8)10). In a recent study, infection with multiple hpV types was also considered an indicator of poor response to radiotherapy (7,11). however, other reports did not demonstrate an association between hpV type and clinical outcome (8,9,12,13).…”