Pretreatment Circulating HPV16 DNA Viral Load Predicts Risk of Distant Metastasis in Patients with HPV16-Positive Oropharyngeal Cancer.

BACKGROUND: There are definite reasons to implement molecular diagnostics based on the measurement of human papillomavirus (HPV) DNA in liquid biopsy into clinical practice. It is a quick, repeatable, and health-safe test for cancer biomarkers in the blood. In this study, we investigated whether the circulating tumor-related HPV16 (ctHPV16) viral load (VL) in patients with oropharyngeal squamous cell carcinoma (OPSCC) was important for determining the risk of locoregional recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS). METHODS: This study included 91 patients with ctHPV16-positive OPSCC who had been treated with radical radiotherapy and chemotherapy. The VL was measured using quantitative PCR (qPCR) and a probe specific for HPV16. Based on 10 years of follow-up, the 2-, 3-, 5-, and 9-year LRFS, MFS, and OS were estimated. RESULTS: The 5-year actuarial LRFS, MFS, and OS rates of patients with ctHPV16-positive/OPSCC were 88%, 90%, and 81%, respectively. The VL was significantly higher in patients who subsequently developed distant metastases (DM) than in those who did not (VL 4.09 vs. 3.25; p = 0.009). In a Cox proportional hazards regression model for MFS, a higher ctHPV16 VL appeared to be a significant independent prognostic factor for the occurrence of DM (HR 2.22, p = 0.015). The ROC curve revealed a cutoff value of 3.556 for VL (p = 0.00001). CONCLUSIONS: A high VL before treatment indicates patients with a significant risk of DM, and should be used in OPSCC treatment stratification.

Determinants of the level of circulating-tumor HPV16 DNA in patients with HPV-associated oropharyngeal cancer at the time of diagnosis.

Circulating tumor HPV DNA (ctHPV16) assessed in liquid biopsy may be used as a marker of cancer in patients with HPV-associated oropharyngeal cancer (HPV + OPC). Factors influencing the initial ctHPV16 quantity are not well recognized. In this study we aimed to establish what factors are related to the level of ctHPV16 at the time of diagnosis. 51 patients (37 men and 14 women, median age of 57 years old) with HPV + OPC prior to definitive treatment were included. ctHPV16 was measured by qPCR. Tumor and nodal staging were assessed according to AJCC8. Blood derived factors included squamous cell carcinoma antigen (SCC-Ag), serum soluble fragment of cytokeratin 19 (CYFRA 21-1), C-reactive protein (CRP), albumin level (Alb), neutrophils (Neut), thrombocytes (Plt) and lymphocyte (Lym) count, Neut/Lym ratio were assessed. The volumes of the primary tumor (TV) and involved lymph nodes (NV) were calculated using MRI, CT or PET-CT scans. Data were analysed using parametric and nonparametric methods. Variables for multivariable linear regression analysis were chosen based on the results from univariable analysis (correlation, univariable regression and difference). There were 9 (18%), 10 (19%) and 32 (63%) patients who had TV and NV assessed in MRI, CT or PET respectively. Primary tumor neither as T-stage nor TV was related to ctHPV16 level. Significant differences in the ctHPV16 between patients with high vs low pain (P = 0.038), NV (P = 0.023), TV + NV (P = 0.018), CYFRA 21-1 (P = 0.002), CRP (P = 0.019), and N1 vs N3 (P = 0.044) were observed. ctHPV16 was significantly associated with CYFRA 21-1 (P = 0.017), N stage (P = 0.005), NV (P = 0.009), TV + NV (P = 0.002), CRP (P = 0.019), and pain (P = 0.038). In univariable linear regression analysis the same variables predicted ctHPV16 level. In multivariable analyses, CYFRA 21-1 and CRP (both as categorical variables) were predictors of ctHPV16 level even above NV. ctHPV16 at presentation is driven by tumor volume measured mostly by N. CYFRA 21-1 and CRP are additional factors related to ctHPV16 prior to the treatment.

Results of Primary Treatment and Salvage Treatment in the Management of Patients with Non-Squamous Cell Malignant Tumors of the Sinonasal Region: Single Institution Experience.

Non-squamous cell carcinoma-related malignant sinonasal tract tumors (non-SCC MSTT) are rare and diverse malignancies. In this study, we report our experience in the management of this group of patients. The treatment outcome has been presented, involving both primary treatment and salvage approaches. Data from 61 patients treated radically due to non-SCC MSTT between 2000 and 2016 at the National Cancer Research Institute, Gliwice branch, were analyzed. The group consisted of the following pathological subtypes of MSTT: adenoid cystic carcinoma (ACC), undifferentiated sinonasal carcinoma (USC), sarcoma, olfactory neuroblastoma (ONB), adenocarcinoma, small cell neuroendocrine carcinoma (SNC), mucoepidermic carcinoma (MEC), and acinic cell carcinoma, which were found in nineteen (31%), seventeen (28%), seven (11.5%), seven (11.5%), five (8%), three (5%), two (3%) and one (2%) of patients, respectively. There were 28 (46%) males and 33 (54%) females at the median age of 51 years. Maxilla was the primary tumor localization followed by the nasal cavity and ethmoid sinus in thirty-one (51%), twenty (32.5%), and seven (11.5%) patients, respectively. In 46 (74%) patients, an advanced tumor stage (T3 or T4) was diagnosed. Primary nodal involvement (N) was found in three (5%) cases, and all patients underwent radical treatment. The combined treatment consisted of surgery and radiotherapy (RT) and was given to 52 (85%) patients. The probabilities of overall survival (OS), locoregional control (LRC), metastases-free survival (MFS), and disease-free survival (DFS) were assessed in pathological subtypes and grouped together, along with the ratio and effectiveness of salvage. Locoregional treatment failure was seen in 21 (34%) patients. Salvage treatment was performed in fifteen (71%) patients and was effective in nine (60%) cases. There was a significant difference in OS between patients who underwent salvage and those who did not (median: 40 months vs. 7 months, p = 0.01). In the group of patients who underwent salvage, OS was significantly longer when the procedure was effective (median: 80.5 months) than if it failed (median: 20.5 months), p < 0.0001. OS in patients after effective salvage was the same as in patients who were primary cured (median: 80.5 months vs. 88 months, p = 0.8). Distant metastases developed in ten (16%) patients. Five and ten year LRC, MFS, DFS, and OS were 69%, 83%, 60%, 70%, and 58%, 83%, 47%, 49%, respectively. The best treatment results were observed for patients with adenocarcinoma and sarcoma, while USC gave the poorest results in our set of patients. In this study, we indicate that salvage is possible in most patients with non-SCC MSTT with locoregional failure and that it may significantly prolong their overall survival.

The Role of Salvage in the Management of Patients with Sinonasal Squamous Cell Carcinoma.

OBJECTIVES: This paper presents and discusses the rate and outcome of salvage according to various factors for patients with sinonasal squamous cell carcinoma (SNSCC). METHODS: Data of 79 patients treated radically due to SNSCC between 2000 and 2016 in the National Cancer Research Institute, Gliwice branch, were analyzed. Surgery was the primary treatment in 63 (79%) of patients. The ratio, type, and effectiveness of salvage was assessed and correlated with prognostic factors. Probabilities of overall survival (OS), local control (LC), nodal control (NC), and locoregional control (LRC) were assessed and compared between the groups. RESULTS: The 5-year LC, NC, and LRC survival rates were 62%, 75%, and 53%, respectively. The 5-year OS rate was 51%. In 34 (43%) patients, treatment failure was reported, and salvage was performed in 17 (50%) of them. It was shown that patients after any salvage had significantly longer 2- and 3-year OS rates when compared to patients with no salvage: 52% vs. 7% and 38% vs. 0%, respectively (p = 0.004). Two- and three-year OS rates for patients after effective and ineffective salvage were 83% vs. 33% and 83% vs. 11%, respectively (p = 0.02). For patients with effective salvage, OS did not differ significantly when compared to the OS of primarily cured patients (p = 0.6). CONCLUSIONS: For SNSCC patients after treatment failure, salvage is possible in half of the cases and can improve their overall survival even if not finally successful. Moreover, effective salvage can compensate for the failure and give the same ultimate OS as in primarily cured patients.