De-Escalating Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma

Economopoulou, Panagiota; Kotsantis, Ioannis; Psyrri, Amanda

doi:10.3390/v13091787

Cited by 15 publications

(10 citation statements)

References 52 publications

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“…Although de-escalation of chemoradiotherapy has been discussed for patients with HPV-associated OPSCC, 35 our results suggest that the therapeutic strategy should be carefully designed depending on the tumor stage. Since the HPV infection rate was <1% in the pure HP/LSCC group, the prognostic significance of HPV infection in these patients is still unclear.…”

Section: Discussionmentioning

confidence: 87%

“…We performed ISH to detect HPV RNA using an E6/E7 mRNA probe set (Advanced Cell Diagnostics) for 18 types of HR-HPV (types 16,18,26,31,33,35,39,45,51,52,53,56,58,59, 66, 68, 73, and 82) with an RNA scope 2.5HD detection kit (Advanced Cell Diagnostics) according to the manufacturer's protocol. Any nuclear or cytoplasmic dots were considered positive.…”

Section: Hpv In Situ Hybridizationmentioning

confidence: 99%

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HPV Infection in Squamous Cell Carcinoma of the Hypopharynx, Larynx, and Oropharynx With Multisite Involvement

Kuga¹,

Yamamoto²,

Jiromaru

et al. 2023

American Journal of Surgical Pathology

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The prevalence and prognostic significance of high-risk human papillomavirus (HR-HPV) have been well-established in oropharyngeal squamous cell carcinoma (OPSCC), but not in hypopharyngeal squamous cell carcinoma (HPSCC) or laryngeal squamous cell carcinoma (LSCC). Moreover, HR-HPV infection in squamous cell carcinoma with multisite involvement has not been examined. To clarify these issues, we retrospectively collected 480 invasive tumors from 467 patients with HPSCC, LSCC, or OPSCC, and comprehensively analyzed the detailed tumor localization, transcriptionally active HR-HPV infection by messenger RNA in situ hybridization, and immunohistochemical staining for p16 and Rb. HR-HPV infection was observed in 115/480 tumors (24%). Human papillomavirus (HPV)-positive cases were closely related with p16 positivity and the partial loss pattern of Rb. HR-HPV was detected in 104 of 161 tumors (64.6%) in the pure OPSCC group and only 1 of 253 tumors (0.4%) in the pure HP/LSCC group; the positive case occurred in the vocal cords. In the multisite-involving combined-type squamous cell carcinoma group, HPV infection was observed in 10/40 (25%) cases, and the 10 HPV-positive cases had OPSCC extending to the larynx or hypopharynx. Among high T-stage (T3/T4) cases of pure OPSCC, HPV-positive cases showed a better prognosis (P=0.0144), whereas the HPV-positive combined OPSCC group did not show a better prognosis (P=0.9428), as compared with HPV-negative counterpart. The results suggest that HR-HPV infection in pure HPSCC and LSCC may be extremely rare. HR-HPV infection seems to be present in a substantial proportion of patients with combined OPSCC and HPSCC/LSCC, but it may not improve prognosis at such advanced disease stages. Confirmation of these points awaits future studies with larger cohorts.

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Section: Discussionmentioning

confidence: 87%

Section: Hpv In Situ Hybridizationmentioning

confidence: 99%

HPV Infection in Squamous Cell Carcinoma of the Hypopharynx, Larynx, and Oropharynx With Multisite Involvement

Kuga¹,

Yamamoto²,

Jiromaru

et al. 2023

American Journal of Surgical Pathology

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“…65 Several studies are ongoing in HPV+ OPC to evaluate different strategies to reduce toxicities while maintaining the high survival rate in this subpopulation of head and neck patients with cancer. 66 The treatment opportunities may be summarized as the use of surgery as the first option to reduce post-operative treatment, the modulation of systemic therapies concurrently to radiation, and the reduction of dose or volume of radiation. Surgical resection and deintensified RT in these patients continues to be an experimental approach, and larger randomized studies are needed.…”

Section: Discussionmentioning

confidence: 99%

Treatment de‐escalation for HPV+ oropharyngeal cancer: A systematic review and meta‐analysis

et al. 2022

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Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV‐counterparts, thereby pushing the adoption of de‐intensification treatment approaches as new strategies to preserve superior oncologic outcomes while minimizing toxicity. We evaluated the effect of treatment de‐intensification in terms of overall survival (OS), progression‐free survival (PFS), locoregional and distant control (LRC and DM) by selecting prospective or retrospective studies, providing outcome data with reduced intensification versus standard curative treatment in HPV+ OPC patients, with a systematic analysis till September 2020. The primary outcome of interest was OS. Secondary endpoints were PFS, LRC, and DM expressed as HR. A total of 55 studies (from 1393 screened references) were employed for quantitative synthesis for 38 929 patients. Among n = 48 studies with data available, de‐intensified treatments reduced OS in HPV+ OPCs (HR = 1.33, 95% CI 1.17–1.52; p < 0.01). In de‐escalated treatments, PFS was also decreased (HR = 2.11, 95% CI 1.65–2.69; p < 0.01). Compared with standard treatments, reduced intensity approaches were associated with reduced locoregional and distant disease control (HR = 2.51, 95% CI 1.75–3.59; p < 0.01; and HR = 1.9, 95% CI 1.25–2.9; p < 0.01). Chemoradiation improved survival in a definitive curative setting compared with radiotherapy alone (HR = 1.42, 95% CI 1.16–1.75; p < 0.01). When adjuvant treatments were compared, standard and de‐escalation strategies provided similar OS. In conclusion, in patients with HPV+ OPC, de‐escalation treatments should not be widely and agnostically adopted in clinical practice, as therein lies a concrete risk of offering a sub‐optimal treatment to patients.

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“…Among the trials of CRT included in the current analysis, only five reported outcomes of interest in patients with p16-positive OPSCC, precluding conclusive results for the exploratory analysis in that subpopulation. Future research can potentially focus on evidence bases other than the one synthesized in the current study; for example, the OS-EFS correlation could be further explored in trials evaluating RT alone in p16-positive patients, particularly those using the de-escalation treatment strategy with lower toxicity rates ( 74 ). Such trials, however, were not directly related to the research questions of the current analysis and were not included in our SLR.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Early Time-to-Event Outcomes and Overall Survival in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving Definitive Chemoradiation Therapy: Systematic Review and Meta-Analysis

Black

Keeping²,

Mojebi³

et al. 2022

Front. Oncol.

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BackgroundOverall survival (OS) is the most patient-relevant outcome in oncology; however, in early cancers, large sample sizes and extended follow-up durations are needed to detect statistically significant differences in OS between interventions. Use of early time-to-event outcomes as surrogates for OS can help facilitate faster approval of cancer therapies. In locally advanced head and neck squamous cell carcinoma (LA-HNSCC), event-free survival (EFS) was previously evaluated as a surrogate outcome (Michiels 2009) and demonstrated a strong correlation with OS. The current study aimed to further assess the correlation between EFS and OS in LA-HNSCC using an updated systematic literature review (SLR) focusing on patients receiving definitive chemoradiation therapy (CRT).MethodsAn SLR was conducted on May 27, 2021 to identify randomized controlled trials assessing radiotherapy alone or CRT in the target population. Studies assessing CRT and reporting hazard ratios (HRs) or Kaplan-Meier data for OS and EFS were eligible for the analysis. CRT included any systemic treatments administered concurrently or sequentially with radiation therapy. Trial-level EFS/OS correlations were assessed using regression models, and the relationship strength was measured with Pearson correlation coefficient (R). Correlations were assessed across all CRT trials and in trial subsets assessing concurrent CRT, sequential CRT, RT+cisplatin, targeted therapies and intensity-modulated RT. Subgroup analysis was conducted among trials with similar EFS definitions (i.e. EFS including disease progression and/or death as events) and longer length of follow-up (i.e.≥ 5 years).ResultsThe SLR identified 149 trials of which 31 were included in the analysis. A strong correlation between EFS and OS was observed in the overall analysis of all CRT trials (R=0.85, 95% confidence interval: 0.72-0.93). Similar results were obtained in the sensitivity analyses of trials assessing concurrent CRT (R=0.88), sequential CRT (R=0.83), RT+cisplatin (R=0.82), targeted therapies (R=0.83) and intensity-modulated RT (R=0.86), as well as in trials with similar EFS definitions (R=0.87), with longer follow-up (R=0.81).ConclusionEFS was strongly correlated with OS in this trial-level analysis. Future research using individual patient-level data can further investigate if EFS could be considered a suitable early clinical endpoint for evaluation of CRT regimens in LA-HNSCC patients receiving definitive CRT.

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De-Escalating Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma

Cited by 15 publications

References 52 publications

HPV Infection in Squamous Cell Carcinoma of the Hypopharynx, Larynx, and Oropharynx With Multisite Involvement

HPV Infection in Squamous Cell Carcinoma of the Hypopharynx, Larynx, and Oropharynx With Multisite Involvement

Treatment de‐escalation for HPV+ oropharyngeal cancer: A systematic review and meta‐analysis

Correlation Between Early Time-to-Event Outcomes and Overall Survival in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving Definitive Chemoradiation Therapy: Systematic Review and Meta-Analysis

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