口腔清洗液中的HPV或可帮助预测口咽癌的复发

  来自约翰霍普金斯大学的研究者通过研究表示，口咽癌患者在癌症治疗后如果唾液中存在人乳头瘤病毒16（HPV16），或可增加其癌症复发的风险；相关研究发表于国际杂志JAMA Oncology上。口咽是喉部上方区域，其包括舌后、软腭、扁桃体及咽喉壁，在美国口咽癌在新发癌症病例中占到了大约2.8%，通常可以通过手术成功治疗该癌症。
  这项研究中，研究者对7%的口咽癌病人在诊断过程中发现了HPV16，随后在接下来的治疗过程中还发现了HPV16的痕迹，同时这些患者在后期生活中癌症都发生了局部复发的情况，该研究或为改善口咽癌患者预后的步骤提供新的思路。实际上所有在治疗后机体中携带有持续性的HPV16的患者出现癌症复发的情况意味着这些HPV16或许可以作为指示患者有效预后的新型工具。
  这项研究中，研究者追踪了124名口咽癌患者，在患者诊断时、随后的疗法后、以及诊断后9个月、12个月、18个月、24个月收集了患者的口服灌洗剂，病人被要求利用漱口水漱口；结果发现，在124名患者中，大约有一半的患者在其癌症诊断时研究者就在其漱口液中发现了HPV16 DNA的存在，而在患者完成治疗后在其口服灌洗液中并未检测到HPV DNA的存在。
  研究者并不清楚如果在治疗后患者的清洗液中发现HPV16的存在，是否就意味着疗法并没有完全清除癌细胞或者癌症又复发了；HPV相关的口咽癌对手术疗法反应较好，但如果癌症扩散了那么手术疗法的成功率就会明显降低，当然研究者希望在患者口服灌洗剂中检测到HPV DNA就可以帮助患者进行癌症复发的早期诊断，这对于改善患者预后将非常关键。
  研究者表示，研究中许多复发患者的复发部位局限于口咽癌部位，而且并没有出现癌症扩散的迹象，而在疗法后检测到口腔中HPV16的存在往往会增加患者口咽癌局部复发的风险。研究者指出，这项研究中患者癌症的复发大约会在口服灌洗剂检出HPV16 DNA后的7个月时开始，而口服灌洗剂中HPV16 DNA的存在同时也可以帮助研究者在患者未出现任何症状之前对其进行诊断，以便及时采取有效的治疗措施。
  最后研究者D'Souza说道，在患者口腔灌洗剂中检出HPV16 DNA到患者癌症复发之间需要几个月时间，如果在检出HPV16 DNA时就采取相应的治疗手段或可有效抑制患者癌症的复发。研究者指出，大部分治疗HPV相关的口咽癌患者都得到了疾病治愈，而且在其口腔中并未检出HPV16 DNA的存在，但这些患者中的部分都出现了疾病复发的迹象，后期我们还需要进行大量研究来开发新型策略来治疗口咽癌复发的患者。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

【1】Prognostic Implication of Persistent Human Papillomavirus Type 16 DNA Detection in Oral Rinses for Human Papillomavirus–Related Oropharyngeal Carcinoma
JAMA Oncol   doi:10.1001/jamaoncol.2015.2524
Eleni M. Rettig, MD1; Alicia Wentz, MA2; Marshall R. Posner, MD3; Neil D. Gross, MD4; Robert I. Haddad, MD5; Maura L. Gillison, MD, PhD6; Carole Fakhry, MD1,2; Harry Quon, MD7; Andrew G. Sikora, MD, PhD8; William J. Stott, CCRP9; Jochen H. Lorch, MD5; Christine G. Gourin, MD1; Yingshi Guo, MS6; Weihong Xiao, MD6; Brett A. Miles, DDS, MD10; Jeremy D. Richmon, MD1; Peter E. Andersen, MD9; Krzysztof J. Misiukiewicz, MD3; Christine H. Chung, MD1,11; Jennifer E. Gerber, MSc12 ; Shirani D. Rajan, MSPH13; Gypsyamber D’Souza, PhD2
Importance  Human papillomavirus–related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear.

Objective  To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival.

Design, Setting, and Participants  Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study.

Main Outcomes and Measures  Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis.

Results  Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months.

Conclusions and Relevance  Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.

【2】Persistent Salivary Human Papillomavirus DNA as a Surveillance Biomarker
Not Just Spitting in the Wind
JAMA Oncol.     doi:10.1001/jamaoncol.2015.2606
Julie E. Bauman, MD, MPH1; Robert L. Ferris, MD, PhD2
Although patients with human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) have a much better prognosis than HPV-negative patients, up to 25% still experience recurrence. Furthermore, efforts to reduce toxic therapy are controversial due to the potential risk for increasing recurrence; thus, early detection of residual or recurrent disease is important to institute salvage therapy.

In this issue of JAMA Oncology, Rettig and colleagues1 show that persistent oral HPV type 16 (HPV16) DNA, measured in pre- and posttreatment rinses of patients undergoing curative-intent therapy for HPV-positive OPSCC, is a harbinger of poor recurrence-free survival. Whereas their data are intriguing, an important clinical question is raised: Does the oral rinse, a noninvasive surveillance tool, identify subclinical local or locoregional recurrence (LRR) at a time amenable to surgical salvage?