Author's personal copy Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer q (original) (raw)
Related papers
Oral Oncology, 2013
Objectives: To describe the natural course of distant metastases (DMs) following radiotherapy (RT) or chemoradiotherapy (CRT) in HPV(+) oropharyngeal carcinoma (OPC). Methods: OPC treated with RT/CRT from 1/1/2000 to 5/31/2010 were reviewed. The natural course of DM were compared between HPV(+) and HPV(À) cohorts. Results: Median follow-up was 3.9 years. The DM rate were similar (11% vs. 15% at 3-years, p = 0.25) between the HPV(+) (n = 457) vs. the HPV(À) (n = 167) cases. While almost all (24/25) HPV(À) DM occurred within 2-years following RT (1 was at 2.1 years), 7/54 (13%) of HPV(+) DM were detected beyond 3 years (up to 5.3 years). Disseminating to >2 organs occurred in 18 (33%) HPV(+) vs. none in HPV(À). Post-DM survival rates were 11% vs. 4% at 2-years (p = 0.02) for the HPV(+) vs. HPV(À) cases respectively. 5/6 HPV(+) with lung oligo-metastasis were still alive with stable disease beyond 2-years after salvage procedures for DM (chemotherapy: 3; surgical resection: 2; radiotherapy: 1). Conclusions: Although DM rates are similar, the natural course of HPV(+) DM differs from that of HPV(À) patients: it may occur after a longer interval, often with a ''disseminating'' phenotype, and a small number may have prolonged survival after salvage for DM.
JAMA Otolaryngology–Head & Neck Surgery, 2015
IMPORTANCE Important differences exist in the pattern and timing of distant metastases between human papillomavirus-initiated (HPV+) and HPV− oropharyngeal squamous cell carcinoma (OPSCC). However, our understanding of the natural history of distant metastases in HPV+ OPSCC and its implications for surveillance is limited. OBJECTIVE To investigate the rate, pattern, and timing of distant metastases in advanced-stage OPSCC treated definitively with concomitant chemoradiotherapy. DESIGN, SETTING, AND PARTICIPANTS In a retrospective review, we identified 291 patients with pathologically diagnosed stages III to IVB OPSCC and known HPV status from a tumor registry at the Cleveland Clinic. Patients were treated from January 1, 1996, through December 31, 2013. Details of treatment failure and the natural history of the disease were retrieved from the electronic medical records. INTERVENTIONS All patients were treated with definitive concomitant chemoradiotherapy. MAIN OUTCOMES AND MEASURES The primary outcome was the rate and timing of distant metastases. Secondary outcomes included the pattern of distant failure and survival after distant metastases. RESULTS Thirty-seven patients developed distant metastatic disease after definitive treatment, including 28 of 252 patients with HPV+ disease and 9 of 39 patients with HPV− disease. The 3-year projected distant control rate was higher in the HPV+ group (88% vs 74%; P = .01). The median time to develop distant metastases was also longer after the completion of treatment for HPV+ disease compared with HPV− disease (16.4 vs 7.2 months; P = .008). We detected a trend in patients with HPV+ disease for more distant metastatic sites involved than in those with HPV− disease (2.04 vs 1.33 sites; P = .09). Although the lung was the most common distant site involved in HPV+ and HPV− disease (HPV+ group, 23 of 28 patients [82%]; HPV− group, 7 of 9 patients [78%]), the HPV+ group had metastases to several subsets atypical for head and neck squamous cell carcinoma, including the brain, kidney, skin, skeletal muscle, and axillary lymph nodes in 2 patients each and in the intra-abdominal lymph nodes in 3 patients. The rate of 3-year overall survival was higher in the HPV+ group (89.9% vs 62.0%; P < .001), as was the median survival after the occurrence of distant metastases regardless of additional treatment (25.6 vs 11.1 months; P < .001). CONCLUSIONS AND RELEVANCE This retrospective review suggests that distant metastases in patients with HPV+ OPSCC occurs significantly later after completion of chemoradiotherapy than in patients with HPV− disease. Human papillomavirus-initiated OPSCC also appears to involve a greater number of subsites and metastatic sites infrequently seen in head and neck squamous cell carcinoma. Distant metastatic disease in HPV+ OPSCC has unique characteristics and a natural history that may require alternative surveillance strategies.
International Journal of Cancer, 2021
We compare outcomes in two large‐scale contemporaneously treated HPV‐positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemoradiotherapy (RT/CRT). p16‐confirmed HPV+ OPC treated between 2007 and 2015 at PMH and DAHANCA were identified. Locoregional failure (LRF), distant metastasis (DM), and overall survival (OS) were compared. Multivariable analysis (MVA) calculated adjusted‐hazard‐ratio (aHR) with 95% confidence interval (95% CI), adjusting for cohort, age, gender, performance status, smoking pack‐years, T‐category and N‐category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM‐8T‐categories (T1‐T2: 77% vs 56%), N‐categories (N0‐N1: 77% vs 67%) and stages (stage I: 63% vs 44% (all P < .001). PMH used standard‐fractionation CRT in 69% (481) while 31% (220) received hypofractionated or moderately accelerated RT‐alone. All DAHANCA patients were treated with moderately accelerated RT; 96% (1129) received nimorazo...
HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer
European Archives of Oto-Rhino-Laryngology, 2008
Prognostic factors are important for treatment decisions as they help adapt the therapy on a case-to-case basis. Nodal status, number of positive nodes, and presence of extracapsular spread are considered to be the important prognostic factors in head and neck cancer. Some studies suggest that human papillomavirus (HPV) status also inXuences the outcome of the treatment. This inXuence can be explained by the variation in tendency to develop regional metastases and by variation in the type of neck node involvement. The study objectives were to compare patients with HPV positive and HPV-negative tumors for survival and prevalence and type of regional metastasis, to identify prognostic factors and to test whether HPV presence is an independent factor of survival. The study included 81 patients treated by surgery including neck dissection for oral or oropharyngeal squamous cell cancer. A computerized medical report was completed for each patient. Analysis of the tumor specimen for the HPV DNA presence was done on paraYn-Wxed tissue. HPV DNA detection and typing were performed by PCR with GP5 + / GP6 + BIO primers and reverse line blot hybridization. Overall, 64% (52/81) of tumors were HPV positive with 80% in the tonsillar site. HPV-positive patients had signiWcantly better both overall (73 vs. 35%) (P = 0.0112) and disease-speciWc (79 vs. 45%) (P = 0.0015) survival rates than HPV-negative patients. No signiWcant diVerences were found in the pN classiWcation, in the number of positive nodes and the presence of extracapsular spread in the involved nodes between HPV positive and HPV-negative tumors. Multivariate analysis showed that signiWcant prognostic factors of survival were the presence of HPV in the tumor, extracapsular spread and tumor size. HPV was the most signiWcant prognostic factor in the studied group of patients with oropharyngeal tumors (HR = 0.27, 95%CI 0.12-0.61) and possibly should be considered in treatment decisions.
Head and Neck Pathology, 2012
To describe the clinical, histopathologic, immunohistochemical and molecular features of human papilloma virus (HPV)? squamous cell carcinomas of the oropharynx that had an atypical clinical course. Methods and Results: Four patients with HPV? oropharyngeal squamous cell carcinoma (OPSCC) were identified retrospectively based on unanticipated clinical behavior. The histopathology, immunohistochemistry and molecular studies of both the primary tumor and the metastases were analyzed to look for any predictors to explain the clinical course. The four patients were all male (average age 55) who presented initially with a neck mass and had stage IVA disease. Three of the primary tumors were nonkeratinizing squamous cell carcinoma and one case was a hybrid tumor of both highgrade squamous cell carcinoma and nonkeratinizing type, and all were p16 and HPV 16/18 positive. All patients received concurrent chemoradiation as primary therapy and had a complete response. Disease-free survival ranged from 7 to 15 months and metastases in 3 patients occurred only in bone, including the sternum, humerus, clavicle, and vertebrae. In one patient, distant metastases were identified in the pancreas, liver, lung and skull base. All metastatic lesions were nonkeratinizing morphology and were p16 and/or HPV positive. Two patients died of their disease, one patient is alive with disease and one patient is disease-free. Although infrequent, unanticipated clinical outcomes can occur in HPV-related OPSCC including distant metastases and boneonly metastases. The tumor morphology of the metastases was comparable to the primary and retained p16 and HPV expression.
Advances in the Management of HPV-Related Oropharyngeal Cancer
Journal of Oncology, 2019
Patients with human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than HPV-negative OPSCC when treated with standard high-dose cisplatin-based chemoradiotherapy. Consistent with this assertion and due to younger age at diagnosis, novel approaches to minimize treatment sequelae while preserving survival outcomes become of paramount importance. Here, we critically reviewed the evidence-based literature supporting the deintensification strategies in HPV-related OPSCC management, including radiotherapy dose and/or volume reduction, replacement of cisplatin radiosensitising chemotherapy, and the use of transoral surgery. Undoubtedly, further researches are needed before changing the standard of care in this setting of patients.
International Journal of Current Research and Review, 2021
Background: Oropharyngeal cancer incidence has been increasing all over the world in the last decades despite advances in various surgical and non-surgical therapies for carcinoma treatment. The incidence of other head and neck cancers are decreasing in the world. It is now established that HPV can be contributed as a part of that increase. Objective: The present trial was aimed to investigate if the oropharyngeal cancer incidence increases with HPV, also to evaluate if the proportion of HPV-positive oropharyngeal cancer patients continues to increase, and if different treatment therapies given to patients with HPV-positive oropharyngeal cancer affect prognosis. Methods: The study was carried out 468 cases of oropharyngeal cancer,88 biopsy samples pre-treatment were available and were analysed with the PCRfrom year 2019-2020 hospital records of various cancer tertiary care centres of the Indian continent. Cases positive for PCR and p16 by immunohistochemistry were finally included in the study. Also, the detection of E7 RNA and E6 of HPV-16 was done, as these are the oncogenes that seem necessary for the oncogenesis process and also contribute to the establishment of the fact that HPV can lead to the carcinomas of the base of the tongue and oropharyngeal base. P16 immunohistochemistry was added as the diagnostic criteria to avoid misdiagnosis/overdiagnosis. Results:66 samples were tested positive for HPV 16, one sample for HPV 33, one sample for HPV 59, and one sample for HPV 35. Three samples out of these 88 were not able to be detected for HPV. mRNA expression for E6 and E7 HPV-16 was detected in all samples except 1 sample. The 88 positive patients were treated with radiotherapy (40), chemoradiotherapy (20), or accelerated radiotherapy (28). No difference was noticed concerning the overall survival rates with the three different treatment modalities used. Conclusion: The results showed that the percentage of HPV positive patients with oropharyngeal cancer increased exponentially from one year to another in consecutive years. No difference was noticed about the overall survival rates with the three different treatment modalities used including radiotherapy, chemoradiotherapy, or accelerated radiotherapy.
International journal of radiation oncology, biology, physics, 2012
To report atypical clinical behavior observed in human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) treated with radiotherapy. A retrospective cohort study was conducted for all newly diagnosed OPC cases treated with radiotherapy on July 1, 2003 to April 30, 2009. HPV positivity was determined by p16 immunostaining in tumors. The incidence of additional malignancies and the pattern of distant metastases (DMs) were compared between the HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. HPV status was evaluated in 318 of 613 consecutive OPC cases (52%), showing 236 HPV+ and 82 HPV- patients. Compared with HPV-, HPV+ cases were less likely to have additional malignancies (prior: 11% vs. 20%, p = 0.038; synchronous: 1% vs. 9%, p = 0.001; metachronous: 6% vs. 16%, p = 0.003). Whereas the majority (10 of 12) of HPV- additional head-and-neck (HN) mucosal malignancies were in the oral cavity, there was none (0 of 7) in the HPV+ cohort (p < 0.001). HPV+ synchronous HN seco...
Unique Patterns of Distant Metastases in HPV-Positive Head and Neck Cancer
Oncology, 2019
Background: HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC) demonstrates favorable outcomes compared to HPV-negative SCC, but distant metastases (DM) still occur. The pattern of DM in HPV+ HNSCC is unclear. Methods: 1,494 HNSCC patients were treated from 2006 to 2012. Recurrence time and metastatic sites in HPV+ HNSCC (Group 1) were compared to patients with HPV-negative/unknown cancers arising in the hypopharynx, larynx, or glottis (Group 2) as well as to patients with HPV-negative/unknown cancers in theoral cavity, oropharynx, hard palate, or tonsil (Group 3). Results: 7/109 (6.4%) patients with HPV+ HNSCC developed DM. The median time to metastases was 11 months. At a median follow-up of 18–25 months, there was no difference in the overall rate of DM for the HPV+ HNSCC group compared to Group 2 (HPV–/unknown) (p = 0.21) and Group 3 (HPV–/unknown) (p = 0.13). There was a significant difference in the rate of DM to the lung in the HPV+ HNSCC group compared to Group ...