In Reference to <i>Should the Contralateral Tonsil Be Removed in Cases of HPV‐Positive Squamous Cell Carcinoma of the Tonsil?</i>

Cognetti, David M.; Topf, Michael C.; Roden, Dylan F.; Luginbuhl, Adam; Curry, Joseph

doi:10.1002/lary.27876

Cited by 4 publications

(19 citation statements)

References 8 publications

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“…The clinical impact of a palatine tonsillectomy in the setting of a contralateral radical tonsillectomy is largely undescribed in the literature, although some subjectively suggest that these patients trend toward increased postoperative pain, dysphagia, bleeding, and readmissions. 12 Dziegielewski et al 10 compared hospital length of stay, gastrostomy tube rates, blood loss, and complications between patients undergoing a radical tonsillectomy alone vs those who also underwent a contralateral tonsillectomy. The only statistically significant finding was greater intraoperative blood loss in the bilateral tonsillectomy group.…”

Section: Discussionmentioning

confidence: 99%

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Systematic Review of Second Primary Oropharyngeal Cancers in Patients With p16+ Oropharyngeal Cancer

Bollig

Lee

Mazul

et al. 2020

Otolaryngol.--head neck surg.

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Objective To systematically review the literature to determine the prevalence and clinical outcomes of second primary oropharyngeal squamous cell carcinoma (OPSCC). Data Sources Search strategies created with a medical librarian were implemented using multiple databases in October 2019. Review Methods The population of interest included adults age >18 years with a p16+ or human papillomavirus-positive OPSCC. The outcome was a synchronous or metachronous second primary OPSCC. Inclusion and exclusion criteria were designed to capture all study designs. In total, 685 records were identified by the search strategy. Two reviewers independently performed the review, extracted data, and performed a quality assessment. Primary Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A random-effects model was used for the meta-analysis. Results A total of 2470 patients with 35 second primary OPSCCs from 15 studies were identified. The pooled prevalence of second primary OPSCC was 1.4% (range, 0%-14.3%). In the random-effects model, the prevalence was estimated at 1.3% (95% CI, 0.7%-2.3%; P = .51, I2 = 52%). Of the 30 patients with treatment information, 26 (86.7%) received surgical treatment, while 4 (13.3%) underwent nonsurgical therapy. Of the 29 patients with available survival information, 22 (75.9%) had no evidence of disease at last follow-up, 5 (17.2%) ultimately died of disease, and 2 (6.9%) were alive with disease. Conclusion Overall, the rate of second primary OPSCC in patients with an index p16+ OPSCC is low, and most patients are successfully treated. Insufficient evidence currently exists to recommend routine elective tonsillectomy during surgical treatment of p16+ OPSCC.

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Section: Discussionmentioning

confidence: 99%

“…11 Some argued that this guideline was not sufficiently substantiated and would only increase morbidity in most patients. 12 Our objective with this study was to systematically review the literature to determine the rate and clinical outcomes of second primary oropharyngeal cancer in patients with an index p161 OPSCC.…”

mentioning

confidence: 99%

Systematic Review of Second Primary Oropharyngeal Cancers in Patients With p16+ Oropharyngeal Cancer

Bollig

Lee

Mazul

et al. 2020

Otolaryngol.--head neck surg.

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“…Opponents argue that addressing one additional subsite while neglecting other subsites in Waldeyer's ring (i.e. the base of tongue) does not provide an oncologic benefit 5,12 . In HPV(+) disease, it has been shown that primary lesions and second primaries are caused by the same viral variant, suggesting that independent inoculation by the same virus can result in field cancerization in the at risk epithelium, or migration of HPV infected cells throughout at risk tissue 14 .…”

Section: Discussionmentioning

confidence: 99%

“…the base of tongue) does not provide an oncologic benefit. 5,12 In HPV(+) disease, it has been shown that primary lesions and second primaries are caused by the same viral variant, suggesting that independent inoculation by the same virus can result in field cancerization in the at risk epithelium, or migration of HPV infected cells throughout at risk tissue. 14 In our study, four (1.1%) metachronous second primaries were found outside of the palatine tonsillar tissue with three in the contralateral base of tongue and one in the soft palate.…”

Section: Discussionmentioning

confidence: 99%

Second Primary Tumors in Patients Presenting With Unilateral HPV‐Associated Tonsillar Squamous Cell Carcinoma

et al. 2021

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Objective: To describe and compare rates of metachronous and synchronous second primaries of the contralateral tonsil in patients with primary HPV(+) tonsillar squamous cell carcinoma (SCC).Study Design: Retrospective cohort study. Materials and Methods: This is a single tertiary care center retrospective case series, from 2006 to 2019, of HPV(+) tonsillar SCC patients who underwent primary surgical resection with unilateral wide-field tonsillectomy or bilateral tonsillectomy for diagnostic or therapeutic purposes. A metachronous second primary is one diagnosed >6 months after completion of surgical treatment. A synchronous second primary is one diagnosed during bilateral tonsillectomy for unilateral HPV(+) tonsillar SCC. Rates of second primary and patient characteristics were compared using chi-square tests.Results: About 303 patients underwent unilateral surgical resection +/À adjuvant therapy for HPV(+) tonsillar SCC. One (0.3%) developed a metachronous second primary in the contralateral tonsil 11.9 years following treatment. Fifty-seven patients with HPV(+) tonsillar SCC underwent bilateral tonsillectomy, and 37/57 (65%) had no clinical signs for contralateral disease. Of these, only 1/37 (2.7%) was incidentally found to have a synchronous second primary. Twenty patients underwent bilateral tonsillectomy due to clinical concern for contralateral disease. Of these, 3/20 (15%) were found to have a synchronous HPV(+) SCC in the contralateral tonsil.Conclusions: The prevalence of metachronous second primary after appropriate treatment of HPV(+) tonsillar SCC is very low (0.3%) and so is the chance of incidentally discovering a synchronous second primary during bilateral tonsillectomy (2.7%). We do not recommend bilateral tonsillectomy as a part of the routine algorithm in the surgical management of these patients.

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“…There is much controversy in the field whether all HPV+ tonsillar carcinoma patients should have their contralateral tonsil removed in order to prevent missing bilateral disease [ 28 ]. Others oppose this idea due to increased morbidity of removing both tonsils and lack of sufficient evidence this would benefit patients, especially given that most patients are given adjuvant radiation and monitored closely so disease in the contralateral tonsil could be caught [ 29 ]. The mechanism behind synchronous bilateral carcinoma development is debated; there is evidence for both clonal expansion of a single primary tumor as well as simultaneous development of independent carcinomas due to similar HPV exposure.…”

Section: Discussionmentioning

confidence: 99%

Viral Integration Analysis Reveals Likely Common Clonal Origin of Bilateral HPV16-Positive, p16-Positive Tonsil Tumors

Pinatti

Walline

Carey

et al. 2020

Arch Clin Med Case Rep

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Infections with high-risk human papilloma viruses (HPV) are responsible for a significant number of oropharyngeal squamous cell carcinoma (OPSCC), with infection rates currently rising at epidemic rates in the western world. Synchronous bilateral HPV+ tumors of both tonsils are a very rare event whose understanding, however, could provide important insights into virus-driven tumor development and progression and whether such integration events are of clonal origin. In this study we analyzed a single case of a bilateral tonsillar p16+ HPV+OPSCC. The viral integration status of the various tumor samples was determined by integration-specific PCR methods and sequencing, which identified viral insertion sites and affected host genes. Integration events were further confirmed by transcript analysis. Analysis of the tumors revealed common viral integration events involving the CD36 gene, as well as a unique event in the LAMA3 gene which resulted in loss of LAMA3 exon one in both tissues that had lost the complex viral LAMA3 integration event. In addition, there were several integration events into intergenic regions. This suggests a common origin but individual evolution of the tumors, supporting the single-clone hypothesis of bilateral tumor development. This hypothesis is further supported by the fact that the two cellular genes LAMA3 and CD36 as targets of viral integration are involved in cell migration and ECM-receptor interactions, which provides a possible mechanism for clonal migration from one tonsil to another.

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In Reference to Should the Contralateral Tonsil Be Removed in Cases of HPV‐Positive Squamous Cell Carcinoma of the Tonsil?

Cited by 4 publications

References 8 publications

Systematic Review of Second Primary Oropharyngeal Cancers in Patients With p16+ Oropharyngeal Cancer

Systematic Review of Second Primary Oropharyngeal Cancers in Patients With p16+ Oropharyngeal Cancer

Second Primary Tumors in Patients Presenting With Unilateral HPV‐Associated Tonsillar Squamous Cell Carcinoma

Viral Integration Analysis Reveals Likely Common Clonal Origin of Bilateral HPV16-Positive, p16-Positive Tonsil Tumors

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