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Semergen Oct 2019Oropharyngeal cancer is in the sixth position of cancer incidence in the world (after colorectal, breast, prostate, bladder, and cervix uteri cancer). More than 90% of... (Review)
Review
Oropharyngeal cancer is in the sixth position of cancer incidence in the world (after colorectal, breast, prostate, bladder, and cervix uteri cancer). More than 90% of them are squamous cell carcinoma. This type of cancer can originate on the lip, oral cavity, pharynx, and larynx. The risk factors associated with oropharyngeal cancer are tobacco, alcohol, and poor oral hygiene. However, other conditions, such as infection with human papilloma virus (HPV) and oral dysbiosis, are gaining prominence. Pre-malignant and malignant lesions are related to diverse factors that can be monitored by the health professional. These professionals are also in an ideal position to influence and advise patients on healthy life habits that contribute to prevent or treat metabolic-endocrine syndromes associated with the development of pre-cancerous disease and cancer located in different organs.
Topics: Carcinoma, Squamous Cell; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Precancerous Conditions; Risk Factors
PubMed: 31079896
DOI: 10.1016/j.semerg.2019.03.004 -
The Laryngoscope Oct 2022Investigate outcomes following oral cavity and oropharyngeal salvage surgery.
OBJECTIVES
Investigate outcomes following oral cavity and oropharyngeal salvage surgery.
METHODS
Adult patients who underwent salvage surgery for recurrent squamous cell carcinoma of the oral cavity and oropharynx from 1996 to 2018 were analyzed using multivariable Cox proportional hazards regression. Disease-free survival (DFS), overall survival (OS), associated factors, and basic quality measures were analyzed.
RESULTS
One hundred and eight patients (72% oral cavity, 28% oropharynx) were followed for a median of 17.9 months. Median DFS and OS were 9.9 and 21 months, respectively. Surgery with adjuvant chemoradiotherapy compared to surgery alone (hazard ratio [HR] = 0.15, 95% confidence interval [CI]: 0.03-0.78) and negative margins (HR = 0.36, 95% CI: 0.14-0.90) were associated with better DFS, while lymphovascular space invasion (LVSI) (HR = 2.66, 95% CI: 1.14-6.19) and higher stage (III vs. I-II, HR = 3.94, 95% CI: 1.22-12.71) were associated with worse DFS. Higher stage was associated with worse OS (HR = 3.79, 95% CI: 1.09-13.19). Patients were hospitalized for a median of 8 days with 24% readmitted within 30 days. A total of 72% and 38% of patients, respectively, underwent placement of a feeding tube or tracheostomy.
CONCLUSIONS
After oral cavity and oropharyngeal salvage surgery, adjuvant chemoradiotherapy, negative margins, negative LVSI, and lower stage were associated with a lower risk of recurrence. Only lower-stage disease was associated with improved survival. The majority of patients had feeding tubes, half underwent free tissue transfer, a third required tracheostomy, and a quarter was readmitted.
LEVEL OF EVIDENCE
3 Laryngoscope, 132:1984-1992, 2022.
Topics: Adult; Humans; Margins of Excision; Mouth; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Retrospective Studies; Salvage Therapy
PubMed: 35191537
DOI: 10.1002/lary.30070 -
Cancer May 2021Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct...
BACKGROUND
Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct pathologic nodal systems. Given that quantitative lymph node (LN) burden is the dominant prognostic factor in most head and neck cancers, we investigated whether HPV- and HPV+ OPC warrant divergent pathologic nodal classification.
METHODS
Multivariable Cox regression models of OPC surgical patients identified via U.S. cancer registry data were constructed to determine associations between survival and nodal characteristics. Nonlinear associations between metastatic LN number and survival were modeled with restricted cubic splines. Recursive partitioning analysis (RPA) was used to derive unbiased nodal schema.
RESULTS
Mortality risk escalated continuously with each successive positive LN in both OPC subtypes, with analogous slope. Survival hazard increased by 18.5% (hazard ratio [HR], 1.19 [95% CI, 1.16-1.21]; P < .001) and 19.1% (HR, 1.19 [95% CI, 1.17-1.21]; P < .001), with each added positive LN for HPV- and HPV+ OPC, respectively, up to identical change points of 5 positive LNs. Extranodal extension (ENE) was an independent predictor of HPV- OPC (HR, 1.55 [95% CI, 1.20-1.99]; P < .001) and HPV+ OPC (HR 1.73 [95% CI, 1.36-2.20]; P < .001) mortality. In RPA for both diseases, metastatic LN was the principal nodal covariate driving survival, with ENE as a secondary determinant. Given the similarities across analyses, we propose a concise, unifying HPV-/HPV+ OPC pathologic nodal classification schema: N1, 1-5 LN+/ENE-; N2, 1-5 LN+/ENE+; N3, >5 LN+.
CONCLUSION
HPV- and HPV+ OPC exhibit parallel relationships between nodal characteristics and relative mortality. In both diseases, metastatic LN number represents the principal nodal covariate governing survival, with ENE being an influential secondary element. A consolidated OPC pathologic nodal staging system that is based on these covariates may best convey prognosis.
LAY SUMMARY
The current nodal staging system for oropharyngeal carcinoma (OPC) has divided human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) OPC into distinct systems that rely upon criteria that establish them as separate entities, a complexity that may undermine the core objective of staging schema to clearly communicate prognosis. Our large-scale analysis revealed that HPV- and HPV+ pathologic nodal staging systems in fact mirror each other. Multiple analyses produced conspicuously similar nodal staging systems, with metastatic lymph node number and extranodal extension delineating the highest risk groups that shape prognosis. We propose unifying HPV- and HPV+ nodal systems to best streamline prognostication and maximize staging accuracy.
Topics: Carcinoma; Humans; Neoplasm Staging; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis
PubMed: 33595897
DOI: 10.1002/cncr.33414 -
Clinical Cancer Research : An Official... Oct 2022Lack of prospectively planned follow-up and minimal characterization of the patient population studied complicate interpretation of circulating human papillomavirus...
Lack of prospectively planned follow-up and minimal characterization of the patient population studied complicate interpretation of circulating human papillomavirus (HPV) DNA as a prognostic biomarker for patients with HPV-associated oropharyngeal carcinoma treated with curative intent. See related article by Berger et al., p. 4292.
Topics: Biomarkers; Carcinoma, Squamous Cell; DNA; Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis
PubMed: 35861851
DOI: 10.1158/1078-0432.CCR-22-1711 -
The Laryngoscope Apr 2021To assess the prognostic value of pre-/post-radiotherapy (pre-/post-RT) radiologic lymph node (LN) features in human papillomavirus (HPV)-positive and HPV-negative...
OBJECTIVES
To assess the prognostic value of pre-/post-radiotherapy (pre-/post-RT) radiologic lymph node (LN) features in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal carcinoma (OPC) patients treated with definitive (chemo-)RT.
METHODS
Clinical node-positive OPCs treated from 2011 to 2015 were reviewed. Nodal features were reviewed by a radiologist on pre-/post-RT computed tomography (CTs). Univariable analysis calculated hazard ratio (HR) for regional failure (RF), distant metastasis (DM), and deaths. Multivariable analysis estimated adjusted HR (aHR) of significant nodal features identified in univariable analysis adjusting for confounders.
RESULTS
Pre-RT CT was undertaken in 344 HPV-positive and 94 HPV-negative OPC patients, of whom 242 (70%) HPV-positive and 67 (71%) HPV-negative also had a post-RT CT. Median follow-up was 4.9 years. Pre-RT LN calcification (pre-RT_LN-cal) increased the risk of RF in HPV-negative (aHR: 5.3, P = .007) but not HPV-positive patients (P = .110). Pre-RT radiologic extranodal extension (pre-RT_rENE+) increased the risk of DM and death in both HPV-negative (DM: aHR 6.6, P < .001; death: aHR 2.1, both P = .019) and HPV-positive patients (DM: aHR 4.9; death: aHR 3.0, both P < .001). Increased risk of RF occured with < 20% post-RT LN size reduction in both HPV-negative (HR 6.0, P = .002) and HPV-positive cases (HR 3.0, P = .049). Post-RT_LN-cal did not affect RF, DM, or death regardless of tumor HPV status (all P > .05).
CONCLUSION
Pre-RT_LN-cal is associated with higher RF risk in HPV-negative but not in HPV-positive patients. Pre-RT_rENE increases risk of DM and death regardless of tumor HPV status. Minimal post-RT LN size reduction (< 20%) increases risk of RF in both diseases. Post-RT_LN-cal + has no apparent influence on outcomes in either disease.
LEVEL OF EVIDENCE
4 (a single institution case-control series) Laryngoscope, 131:E1162-E1171, 2021.
Topics: Adult; Aged; Aged, 80 and over; Extranodal Extension; Female; Humans; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 33002201
DOI: 10.1002/lary.29045 -
Current Treatment Options in Oncology Jan 2022Human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in incidence, and has now become the most common head and neck... (Review)
Review
Human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in incidence, and has now become the most common head and neck cancer (HNC). Studies have demonstrated that HPV associated OPSCC is associated with a favorable prognosis compared with its HPV-negative counterparts, yet standard multimodality therapy is often associated with substantial acute and late treatment-related toxicity. While locoregional control is improved in HPV+ OPSCC, distant metastasis rate has gained recognition as a major cause of death in this population, with some studies suggesting similar rates as non-HPV-related cancers. Induction chemotherapy has been of long-standing interest in locoregionally advanced HNC, yet its use in combination with concomitant chemoradiation remains an area of controversy as a survival benefit remains unproven following randomized trials. Nevertheless, response to induction chemotherapy remains an important dynamic and prognostic biomarker, with response-adaptive de-intensified therapy in HPV+ OPSCC gaining traction in single-arm phase II studies demonstrating promising results. The emergence of immunotherapy in the recurrent/metastatic setting for HNC has led to enthusiasm to incorporate in the curative setting, yet its role remains undefined. Our institutional paradigm for HPV+ OPSCC incorporates induction therapy followed by risk and response adaptive locoregional treatment. Ultimately, the role of induction therapy in HPV+ OPSCC will need to be investigated in a randomized setting to be incorporated routinely into clinical practice.
Topics: Head and Neck Neoplasms; Humans; Induction Chemotherapy; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 35171457
DOI: 10.1007/s11864-022-00941-9 -
Clinical Cancer Research : An Official... Oct 2022Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence....
PURPOSE
Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence. Current posttreatment surveillance practices rely on physical examinations and imaging and are inconsistently applied. We assessed circulating tumor tissue modified viral (TTMV)-HPV DNA obtained during routine posttreatment surveillance among a large population of real-world patients.
EXPERIMENTAL DESIGN
This retrospective clinical case series included 1,076 consecutive patients across 108 U.S. sites who were ≥ 3 months posttreatment for HPV-driven OPSCC and who had one or more TTMV-HPV DNA tests (NavDx, Naveris Laboratories) obtained during surveillance between February 6, 2020, and June 29, 2021. Test results were compared with subsequent clinical evaluations.
RESULTS
Circulating TTMV-HPV DNA was positive in 80 of 1,076 (7.4%) patients, with follow-up available on all. At first positive surveillance testing, 21 of 80 (26%) patients had known recurrence while 59 of 80 (74%) patients were not known to have recurrent disease. Among these 59 patients, 55 (93%) subsequently had a confirmed recurrence, 2 patients had clinically suspicious lesions, and 2 had clinically "no evidence of disease" (NED) at last follow-up. To date, the overall positive predictive value of TTMV-HPV DNA testing for recurrent disease is 95% (N = 76/80). In addition, the point-in-time negative predictive value is 95% (N = 1,198/1,256).
CONCLUSIONS
These findings highlight the clinical potential for circulating TTMV-HPV DNA testing in routine practice. As a surveillance tool, TTMV-HPV DNA positivity was the first indication of recurrence in the majority of cases, pre-dating identification by routine clinical and imaging exams. These data may inform future clinical and guideline-endorsed strategies for HPV-driven malignancy surveillance. See related commentary by Colevas, p. 4171.
Topics: Alphapapillomavirus; Biomarkers; DNA, Viral; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 35576437
DOI: 10.1158/1078-0432.CCR-22-0562 -
Cancer Journal (Sudbury, Mass.)The global incidence of human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surged in recent decades, with HPV+ HNSCC accounting for... (Review)
Review
The global incidence of human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surged in recent decades, with HPV+ HNSCC accounting for >70% of oropharynx cancers in the United States. Its incidence in men has surpassed that of HPV+ cervical cancer in women, and reliable assays are needed for early detection and to monitor response to therapy. Human papillomavirus-positive OPSCC has a more favorable response to therapy and prognosis than HPV-negative (HPV-) HNSCC, motivating regimens to deintensify curative surgery or chemoradiotherapy protocols. A barrier to deintensifying and personalizing therapy is lack of reliable predictive biomarkers. Furthermore, HPV- HNSCC survival rates are static without reliable surveillance biomarkers available. The emergence of circulating plasma-based biomarkers reflecting the tumor-immune microenvironment heralds a new era in HNSCC diagnosis and therapy. We review evidence on tumor-derived extracellular vesicles (exosomes) as biomarkers for diagnosis, prognostication, and treatment in HPV+ and HPV- HNSCC.
Topics: Male; Female; Humans; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Human Papillomavirus Viruses; Carcinoma, Squamous Cell; Papillomavirus Infections; Exosomes; Oropharyngeal Neoplasms; Biomarkers; Liquid Biopsy; Tumor Microenvironment
PubMed: 37471614
DOI: 10.1097/PPO.0000000000000671 -
Otolaryngologic Clinics of North America Dec 2020Transoral robotic surgery is a useful minimally invasive technique in the treatment of oropharyngeal squamous cell carcinoma, both human papilloma virus (HPV)-positive... (Comparative Study)
Comparative Study Review
Transoral robotic surgery is a useful minimally invasive technique in the treatment of oropharyngeal squamous cell carcinoma, both human papilloma virus (HPV)-positive and HPV-negative patients in certain instances. This treatment modality often has proven useful for certain tumor persistences or recurrences. Good outcomes are possible given appropriate patient selection, both oncologically and functionally.
Topics: Carcinoma, Squamous Cell; Humans; Natural Orifice Endoscopic Surgery; Oropharyngeal Neoplasms; Papillomaviridae; Robotic Surgical Procedures; Treatment Outcome
PubMed: 32854946
DOI: 10.1016/j.otc.2020.07.010 -
Journal of Zhejiang University....Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human... (Review)
Review
Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.
Topics: Alphapapillomavirus; Cyclin-Dependent Kinase Inhibitor p16; Immunohistochemistry; In Situ Hybridization; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Oropharyngeal Neoplasms; Polymerase Chain Reaction; Squamous Cell Carcinoma of Head and Neck
PubMed: 33843162
DOI: 10.1631/jzus.B2000161