Unilateral radiotherapy treatment for p16/human papillomavirus–positive squamous cell carcinoma of unknown primary in the head and neck

Tiong, Albert; Rischin, Danny; Young, Richard J.; Herschtal, Alan; Solomon, Benjamin; D’Costa, Ieta; Fua, Tsien; Liu, Chen; Coleman, Andrew; Kleid, Stephen; Dixon, Benjamin J.; Corry, June

doi:10.1002/lary.27131

Cited by 16 publications

(29 citation statements)

References 48 publications

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“…6,16,17,20 The male predominance correlates with the ease of female-to-male HPV transmission which is precipitated by the high number of sexual partners and oral sex encounters. 16,17,19,20,[22][23][24] However, one retrospective analysis of a small series of patients showed that the HPV status does not correlate with neck stage at presentation. The clinical N classification at diagnosis is usually N2/N3 (11%-95%).…”

Section: Clinical Presentationmentioning

confidence: 99%

“…The assessment for HPV and p16 must be performed systematically on FNAC in patients with SCCUP as their positivity raises the suspicion of a primary oropharyngeal squamous cell carcinoma (OPSCC). 7,16,23,24,54 Different tools for the detection of biologically active HPV infections have been evaluated in SCCUP. 16,17,51,52 The predominant pathology in HPV-related SCCUP is the non-keratinizing basaloid squamous cell carcinoma with occasional necrosis.…”

Section: Pathology and Hpv Assessmentmentioning

confidence: 99%

“…79,80 Unfortunately, these studies did not report specific data on patients with HPV-related SCCUP. 23,54,68,69 Ipsilateral radiotherapy seems well tolerated with acceptable toxicity, which includes dysgeusia, salivary alteration, and skin erythema that reversed after symptomatic treatment. 23,54,68,69 Ipsilateral radiotherapy seems well tolerated with acceptable toxicity, which includes dysgeusia, salivary alteration, and skin erythema that reversed after symptomatic treatment.…”

Section: Radiation With or Without Concomitant Chemotherapymentioning

confidence: 99%

“…23,54,68,69 Ipsilateral radiotherapy seems well tolerated with acceptable toxicity, which includes dysgeusia, salivary alteration, and skin erythema that reversed after symptomatic treatment. 23,81 Ninety percent of patients rated their health-related quality of life as very good. 23,81 Ninety percent of patients rated their health-related quality of life as very good.…”

Section: Radiation With or Without Concomitant Chemotherapymentioning

confidence: 99%

“…82 Mucosal irradiation was a common practice in the past but the larynx and hypopharynx are currently spared because recurrences are rare at these sites. 23 71,83 In one study of 80 patients with SCCUP (18 HPV-related SCCUP), 75 patients underwent elective RT (46 Gy in 2 Gy/fraction) of the full upper aerodigestive mucosa with none experiencing local recurrence.…”

Section: Radiation With or Without Concomitant Chemotherapymentioning

confidence: 99%

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Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

2019

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Background Human papillomavirus (HPV)‐related squamous cell carcinoma of unknown primary (SCCUP) is currently rising in incidence but lacks a validated management approach. Aims This paper reviews the clinical presentation, diagnosis, and treatment of HPV‐related SCCUP. Materials and Methods The Medline/Pubmed database was searched by using the following keywords “CUP”, “cancer of unknown primary”, “HPV”, “human papilloma virus”, and “head and neck”. The references of the publications of interest were also screened for relevant papers. Results The clinical assessment of HPV‐related SCCUP includes a complete clinical examination, an endoscopic evaluation with white‐light and narrow band imaging, and radiologic assessment using morphologic and metabolic imaging. If the diagnosis remains unconfirmed, endoscopic examination under anesthesia with tonsillectomy ± base of tongue mucosectomy is performed. The therapeutic rationale aims to eradicate the involved lymph nodes and potential primary tumor with a sequence of chemoradiotherapy and neck dissection. Discussion As a general approach, p16‐negative SCCUP are truly HPV negative, whereas p16‐positive specimens require confirmation with HPV in situ hybridization or polymerase chain reaction to confirm HPV infection. If a cervical metastasis is considered HPV positive, the primary lesion is likely in the oropharynx, and further diagnostic interventions such as tonsillectomy seems to be mandatory. Whether the optimal treatment is neck dissection followed by adjuvant radiotherapy or concomitant chemoradiotherapy (CRT) (in case of extranodal extension or advanced lymph node stages) or definitive CRT followed by neck dissection (in case of positive 18F‐FDG‐PET/CT) remains a matter of debate. Solid scientific evidence supporting treatment de‐escalation in HPV‐related SCCUP is lacking, and the results of ongoing trials are at the brink of reporting. Conclusion Currently, the treatment of patients with HPV‐related SCCUP should not differ from the standard treatment of other SCCUP patients and is similarly based on the staging of the disease and general condition of the patient.

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Section: Clinical Presentationmentioning

confidence: 99%

Section: Pathology and Hpv Assessmentmentioning

confidence: 99%

Section: Radiation With or Without Concomitant Chemotherapymentioning

confidence: 99%

Section: Radiation With or Without Concomitant Chemotherapymentioning

confidence: 99%

Section: Radiation With or Without Concomitant Chemotherapymentioning

confidence: 99%

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Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

2019

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Human papillomavirus and p16 immunostaining, prevalence and prognosis of squamous carcinoma of unknown primary in the head and neck region

Ren

Wen

et al. 2019

Intl Journal of Cancer

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Science searches, observational studies and clinical trials that reported survival rates of patients with SCCUPHN by HPV status were identified. Meta-analysis estimated the prevalence and prognosis (overall survival, OS; progression-free survival, PFS) of SCCUPHN by HPV status, and compared them to studies of oropharyngeal squamous cell carcinoma (OPSCC) from the same institutions and across continents. In 17 SCCUPHN studies (n = 1,149) and 17 institution-matched OPSCC studies (n = 6,522), the pooled HPV prevalence of SCCUPHN was 49%, which was only 10% (95%CI: 1-19%) lower than OPSCC prevalence in the underlying population. Estimated 5-year OS for HPV-negative SCCUPHN was 44% (95%CI: 36-51%) vs. HPV-positive SCCUPHN of 91% (95%CI: 86-96%); hazard ratio (HR) for OS was 3.25 (95%CI: 2.45-4.31) and PFS was 4.49 (95%CI: 2.88-7.02). HRs by HPV status for OPSCC were similar to that in SCCUPHN. While North American SCCUPHNs had higher HPV prevalence than European SCCUPHNs (OR = 2.68 (95%CI: 1.3-5.6)), HR of OS for HPV-negative vs. HPV-positive patients were similar in both continents (HRs of 3.78-4.09). Prevalence of HPV among SCCUPHN patients were lower than in OPSCC. The survival benefit conferred by being HPV-positive was similar in SCCUPHN as in OPSCCs, independent of continent.

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Pharyngeal‐sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work‐up

Grewal

Rajasekaran²,

Cannady³

et al. 2019

The Laryngoscope

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Objective In patients with head and neck carcinoma of unknown primary (HNCUP;pT0) following TORS‐assisted workup, we have adopted a pharyngeal‐sparing radiation therapy (PSRT) approach targeting only the at‐risk neck and omitting treatment of the pharynx. We report outcomes following PSRT, and compare to institutional historical control subjects who received pharyngeal‐targeted RT (PRT). Methods Between 2009 and 2018, 172 patients underwent TORS‐assisted endoscopy as part of their workup for HNCUP. Following TORS, 54 patients had pT0 disease, of which 45 received RT. Forty‐nine percent received PSRT and 51% received PRT. Results No statistically significant differences existed between the PSRT and PRT groups with respect to overall nodal distribution, p16 positivity (55% vs. 43%, P = .12), neck dissection rates (77% vs. 65%, P = .51), and administration of chemotherapy (55% vs. 65%, P = .55). Median follow‐up for PSRT and PRT groups were 24 and 28 months, respectively (P = .04). Two‐year RFS was 86% and 74% for PSRT and PRT patients, respectively (log‐rank P = .30). Three and six patients recurred after PSRT and PRT, respectively. Two‐year OS for PSRT and PRT patients was 91% and 74%, respectively (log‐rank P = .31). Compared to PRT, PSRT was associated with statistically significantly less: grade 2+ mucositis (18% vs. 91%, P < .01), new opioid requirement (27% vs. 91%, P < .01), mean weight loss during RT (6.2 lbs vs. 17.4 lbs, P < .01), feeding tube placement during RT (5% vs. 43%, P < .01), and treatment‐related unplanned hospitalizations (9% vs. 39%, P = .04). Conclusion Following TORS‐assisted management of patients with pT0 HNCUP, we observed reduced toxicity following PSRT compared to PRT without apparent compromise of disease cure. Level of Evidence Level 3 evidence, retrospective review comparing cases and controls Laryngoscope, 130:691–697, 2020

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Unilateral radiotherapy treatment for p16/human papillomavirus–positive squamous cell carcinoma of unknown primary in the head and neck

Abstract: 4 Laryngoscope, 128:2076-2083, 2018.

Cited by 16 publications

References 48 publications

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

Human papillomavirus and p16 immunostaining, prevalence and prognosis of squamous carcinoma of unknown primary in the head and neck region

Pharyngeal‐sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work‐up

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