Association between tonsillectomy and risk of oropharyngeal cancer: a systematic review.

Objective: Studies have demonstrated that tonsillectomy may alter the risk of oropharyngeal cancer (OPC). We systematically reviewed the evidence and pooled data to examine such an association. Methods: PubMed, Embase, and Scopus were searched up to 25th April 2023. Studies reporting an association between tonsillectomy and oropharyngeal cancer risk at any site were included. Results: Five studies were eligible. All examined the risk of tonsillar and base of the tongue (BOT) cancer with prior history of tonsillectomy. On meta-analysis of the data, prior history of tonsillectomy was associated with a significantly decreased risk of tonsillar cancer. The second meta-analysis showed that history of tonsillectomy did not significantly alter the risk of BOT cancer. However, after exclusion of one study, the results showed an increased risk of BOT cancer with a history of tonsillectomy. Conclusions: The scarce data available in the literature suggests that tonsillectomy may reduce the risk of tonsillar cancer but does not alter the risk of BOT cancer. Further studies are needed to explore the association between tonsillectomy and the risk of OPC.

[Tonsillar asymmetry in adults: review of the literature and management algorithm]. / Asymétrie amygdalienne chez l'adulte: revue de littérature et proposition de prise en charge.

Tonsillar asymmetry is both a common clinical finding and a potential sign of cancer. The diagnosis of the latter requires tonsillectomy, which is associated with two weeks off work and post-operative risk of bleeding, which ranges between 1.5 and 15% of the cases. Thus, it is crucial to determine which patients can be followed clinically and which ones will need a diagnostic tonsillectomy. This article provides a review of the literature on tonsillar asymmetry in the adult population and an algorithm for its management.

L'asymétrie amygdalienne est à la fois une découverte clinique fréquente et un potentiel signe de cancer. Le diagnostic de ce dernier se pose par une amygdalectomie. Celle-ci est associée à un arrêt de travail d'environ deux semaines, ainsi qu'à des risques postopératoires de saignement qui varient de 1,5 à 15% des cas. Il est donc crucial de déterminer quels patients peuvent être suivis cliniquement et quels sont ceux qui doivent bénéficier d'une amygdalectomie diagnostique. Cet article propose une revue de la littérature sur l'asymétrie amygdalienne dans la population adulte ainsi qu'un algorithme de prise en charge.

Association of Human Papillomavirus and Epstein-Barr Virus Infection with Tonsil Cancer in Northeastern Thailand.

BACKGROUND: Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are associated with head and neck cancer, including tonsil cancer (TC) in the oropharyngeal area. Increasing incidence of HPV and EBV infection in different cancer tissues of oropharynx in both epithelial and lymphoid tissues, have been reported. However, little is known about association of these tumor viruses with TC in the Thai population. Here, we investigated the prevalence of HPV and EBV infection in different histology of TC and their association with TC from Thai patients. METHODS: Eighty-three exfoliated tonsil cells from non-cancer controls (NCC) and 65 formalin-fixed paraffin-embedded TC tissues (TC) that were histologically classified as tonsillar squamous-cell carcinoma (TSCC) or diffuse large B-cell lymphoma (DLBCL) were studied. Prevalence of HPV and EBV infection was determined by real-time PCR. HPV genotyping was performed by reverse line blot hybridization and HPV genome status was investigated by multiplex qPCR. Localization of EBV infection was determined by EBER in situ hybridization. RESULTS: Infection of HPV and EBV in TC cases was 16.9% and 30.8%, whereas in exfoliated tonsil cells was 1.2% and 66.3% respectively. HPV infection was significantly higher in TSCC (30.6%) than DLBCL samples (13.8%). HPV58 was commonly detected and presented as an integrated form in TSCC, whereas only episomal form was found in DLBCL. EBV infection was significantly higher in DLBCL (44.8%) than TSCC samples (19.4%), and detected in both lower than among exfoliated tonsil cell samples (66.3%). By EBER in situ hybridization in TSCC, EBV infection localized both in epithelial cells and infiltrating lymphocytes. The co-occurrence of HPV and EBV infection was 11.11% and 13.79% of TSCC and DLBCL, respectively, was associated with well-differentiated TSCC. CONCLUSION: HPV and EBV infection was significantly involved in a specific TC tissue, and associated with a good clinical outcome in TSCC.

Incidence of synchronous contralateral tonsillar malignancy in a known case of unilateral tonsillar carcinoma.

OBJECTIVE: The literature is divided with regards to contralateral tonsillectomy in a known/suspected case of ipsilateral tonsillar malignancy. In this study, we evaluate the incidence of indolent synchronous contralateral tonsillar malignancy (SCTC) in patients with known ipsilateral tonsillar malignancy. METHODS: All patients diagnosed with ipsilateral tonsillar carcinoma (TC) at a tertiary teaching center between January 2016 and December 2019 were screened. None of the patients were suspected to have bilateral TC. All patients underwent appropriate imaging in the form of Magnetic resonance imaging and computed tomography of head and neck region and then underwent bilateral tonsillectomy. The prevalence of bilateral tonsillar malignancy and the factors predicting them were analyzed. RESULTS: In all 59 patients were included in the study. The mean and median age of the patient population was 60.8 and 59 years, respectively, with a male to female ratio of 3.2:1. The incidence of bilateral tonsillar malignancy in carcinoma of unknown primary (CUP) was 3/10 (33.3%). Among the remaining 49 patients, incidence of synchronous contralateral tonsillar carcinoma (SCTC) was 2/49 (4.08%). Overall, 5/59 (8.5%) patients had synchronous bilateral tonsillar malignancy. Furthermore, dysplasia was found in the contralateral tonsil in 4/10 (40%) CUP patients. Among the remaining 49 patients, dysplasia was seen in the contralateral tonsil in 20/49 (40.8%) patients. The absence of p16 expression predicted higher probability of SCTC. Factors like gender, T stage, nodal status or smoking did not predict SCTC. CONCLUSION: We recommend bilateral tonsillectomy in all patients with suspected or proven TC (unilateral or bilateral) and CUP as it helps identify indolent SCTC and it does not add any significant morbidity to the patients. LEVEL OF EVIDENCE: III.

Prevalence and characteristics of tonsillar human papillomavirus infection in tumor-free patients undergoing tonsillectomy.

OBJECTIVE: This study evaluated the prevalence and characteristics of tonsillar human papillomavirus (HPV) infection in tumor-free patients undergoing tonsillectomy. METHODS: We prospectively enrolled healthy patients who underwent tonsillectomy for tumor-free tonsillar disease. Their tonsillar HPV infections were evaluated using CLART HPV2, and subsequent p16 immunohistochemistry was performed in patients with positive HPV infection. Moreover, the results of tonsillar HPV infection were analyzed according to sex, age, and indication of tonsillectomy. RESULTS: A total of 362 patients were included. HPV test was positive in 8 patients, with an overall prevalence of 2.2%. All detected HPV types were high-risk, including HPV 16 in six patients, HPV 52 in one patient, and HPV 58 in one patient. P16 was negative in all 8 patients with HPV infection. The prevalence of tonsillar HPV infection in males and females was 2.4% (6/246) and 1.7% (2/116), respectively (P > 0.999), and in pediatric and adult patients, 2.2% (5/228) and 2.2% (3/134), respectively (P > 0.999). The prevalence showed a bimodal peak at 1st and 6th decades, with the prevalence of 2.6% (5/194) and 7.9% (3/38), respectively. The prevalence of tonsillar HPV infection in tonsillitis and non-tonsillitis groups were 0.0% (0/104) and 3.1% (8/258), respectively (P = 0.111). CONCLUSION: The prevalence of tonsillar HPV infection in tumor-free patients was low, but all detected HPV infections were high-risk types. Our results support using a 9-valent vaccine which covers all high-risk HPV types found in this study.

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

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 +/- 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. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:332-338, 2022.

Epidemiologic distinctions between base of tongue and tonsil oropharyngeal carcinomas.

BACKGROUND: Human papillomavirus (HPV)-positive tonsil and base of tongue (BOT) cancers have been considered together. However, important differences may exist. METHODS: Demographic and tumor characteristics, and survival, were compared by oropharyngeal cancer subsite from 2004 to 2016 in the National Cancer Database (NCDB). Trends in tonsillectomy from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were examined. RESULTS: HPV-positive BOT (N = 13 081) were older than HPV-positive tonsil patients (N = 16 874; mean 61.5 vs. 58.4 years, p < 0.001), and individuals 70+ years were significantly more likely to have BOT tumors compared with individuals <50 (adjusted odd ratio [aOR] = 2.9, 95% confidence interval = 2.6-3.2). BOT patients were also more likely to be white, male, and have advanced tumor classification. Among 7418 NHANES participants, tonsillectomy was associated with older age and white race. CONCLUSIONS: There are epidemiologic and tumor-related differences among HPV-positive tonsil and BOT carcinomas. Demographic differences may be attributable to tonsillectomy trends.

Tonsillectomy as a Prevention Strategy in the Light of Increasing Incidence of Oropharyngeal Cancer - a Research of Current Literature.

BACKGROUND/AIM: While in many Western countries the number of tonsillectomies decreases significantly, there is an increasing incidence of oropharyngeal carcinomas. For, obviously, removal of the tonsils will reduce individual risk for tonsil cancer, the question of tonsillectomy as a prevention strategy is suggested. This study focused on this question by carrying out a literature research. MATERIALS AND METHODS: A literature research was performed (www.pubmed.gov; Search words: tonsillectomy, oropharyngeal cancer, tonsil cancer, prevention) without applying additional filters. RESULTS: Out of the 16 identified studies, three population-based studies were evaluated. Individual incidence of tonsil cancer is significantly lower after removal of tonsils; however, risk elimination by tonsillectomy has not been proven. One of the studies revealed increasing numbers of base of the tongue cancer after previous tonsillectomy. CONCLUSION: The increase in oropharynx carcinomas can currently be attributed not to the decreasing tonsillectomy rates, but to the increase in HPV infections. A previous tonsillectomy reduces the individual risk of developing tonsil carcer. Tonsillectomy as prevention for oropharyngeal cancer cannot be recommended and may even be a disadvantage concerning base of the tongue cancers.

Occult Malignancy in Adult Tonsillectomy for Benign Indication.

OBJECTIVE: National pathology guidelines recommend full pathologic analysis for all adult tonsillectomy specimens. We evaluated the available data on occult malignancy in adult tonsillectomy for benign indication, and created a screening system to reduce the risk of missed malignancies if routine histopathologic examination were to be discontinued. STUDY DESIGN: Retrospective chart review and systematic review of the literature. SETTING: Tertiary care academic hospital and multi-hospital private healthcare system. SUBJECTS AND METHODS: A systematic literature review identified case series of adult tonsillectomy. Retrospective chart review at our institutions from 2000 to 2016 produced an additional case series. The pooled rate of occult malignancy was determined, and re-analyzed using criteria based on preoperative risk factors designed to identify patients requiring full pathologic analysis. The predicted effects of prospective application of the proposed criteria were calculated. Pooled occult malignancy prevalence was estimated. RESULTS: Literature review and our own case series yielded 12,094 total cases. Occult malignancy prevalence in the combined data was 0.033%, representing four occult malignancies. Three out of the four would have been selected for full pathology preoperatively with use of the proposed criteria. Statistical analysis indicates that the predicted frequency of occult malignancy incidence in cases negative for the criteria is 0.01%, or 1/10,000. CONCLUSION: Application of the proposed criteria to adults undergoing tonsillectomy for benign indication identifies a subset of patients with an estimated incidence of occult malignancy similar to that reported for pediatric tonsillectomy, and potentially may permit safe elimination of pathologic analysis of their tonsil specimens. LEVEL OF EVIDENCE: Pooled analysis of case series from the literature and a single institution, level 4.

No association between HPV-status in tonsillar tissue and sexual behavior of the patients in a northern German population - Critical view of the link between HPV natural history and HPV-driven carcinogenesis.

HPV-infection in patients with HNSCC is reportedly correlated with sexual behavior, age, and tobacco/alcohol-consumption. HPV-infections of the oral cavity are regarded as sexually transmitted. Comparable data of patient populations outside the U.S. are sparse or missing. Questionnaires regarding sexual behavior, education tobacco- and alcohol-consumption, were given to 28 patients with tonsillar hyperplasia (H) and 128 patients with tonsillar carcinomas (CA), all with tissue-typed HPV-DNA-status performing PCR. Answers were correlated among groups and HPV-status. 106 questionnaires were analyzed. Comparisons between H- (n = 25) and CA- (n = 81) patients showed that CA-patients were older (61.1yrs ± 9.3) than H-patients (45.2yrs ± 11.9; p < 0.0001; Student's t-test); had a lower educational level (p = 0.0095); and lower number of sexual partners (p = 0.0222; Fisher's exact test). All groups showed a significant correlation between smoking and lack of HPV-DNA-positivity (p = 0.001). Further Fisher's exact tests and logistic regression analysis revealed in all 106 patients no significant correlations between tissue-HPV-status and the analyzed parameters. Despite the limited sample size, we were able to confirm the established correlation between smoking and tissue-HPV-status. The correlation between sexual behavior and HPV-infection was not confirmed. No consensus exists in the literature about the latter. Our data does not support the strict classification of oral HPV-infections and HPV-driven HNSCCs as STDs.

Human papillomavirus (HPV) in Chinese oropharyngeal squamous cell carcinoma (OPSCC): A strong predilection for the tonsil.

OBJECTIVE: Compared with Occident's data, the incidence of Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) had been reported as relatively low in Mainland China. The objective of this study was to report the integrated prevalence of HPV and Epstein-Barr virus (EBV), and further evaluate the different behaviors of HPV-positive and -negative OPSCCs in eastern China. METHODS: In a cohort of 170 nonmetastatic OPSCCs treated from January 2007 to July 2019, p16 protein expression, HPV genotypes, and Epstein-Barr virus-encoded RNA (EBER) were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). The clinical and pathologic findings were further collected and analyzed to comprehensively reveal the behaviors of Chinese OPSCCs. RESULTS: Out of the 170 tumor tissues evaluated, 57.6% (98) samples had positive p16 expressions. A total of 65.1% (99/152) samples had positive HPV genotypes, besides HPV16 (92/152), HPV11, 18, 33, 53, and 58 were also detected. The positive rate of EBER was 7.2% (9/124), and the co-infection rate of EBV/HPV was 4.0%. Related to the unequal distributions of p16 expression, HPV-related tumors arisen from tonsillar and non-tonsillar accounted for 68.8% (75/109) and 37.7% (23/61) of their cases, respectively (P < .001). With a median follow-up time of 13.1 months, significant survival advantages of HPV-related OSPCC were observed; 1-year OS, PFS, RFS, and MFS were 83.2% vs 96.7% (P < .001), 71.6% vs 96.2% (P < .001), 77.7% vs 96.2% (P = .002), and 90.4% vs 100.0% (P = .024) in p16-negative and -positive cases, respectively. CONCLUSIONS: The relative percent of HPV-positive OPSCCs in this study is close to the positive rate in many Western countries and a strong predilection was discovered for the tonsillar. The EBV infection and co-infection of HPV/EBV were largely low. The prognosis of HPV-positive OSPCCs was more favorable than its negative counterpart.

A global epidemic increase of an HPV-induced tonsil and tongue base cancer - potential benefit from a pan-gender use of HPV vaccine.

In 2007, human papillomavirus (HPV) type 16 was finally recognized as a risk factor, besides smoking and alcohol, for oropharyngeal squamous cell carcinoma (OPSCC), including tonsillar squamous cell carcinoma (TSCC), by the International Agency for Research against Cancer. Just before, in 2006, the Food and Drug Administration had approved Gardasil, the first vaccine against HPV16, 18, 6 and 11, for preventive vaccination women against cervical cancer. Concurrently, some Western countries, where smoking was decreasing, disclosed an epidemic increase in the incidence of OPSCC, especially of TSCC and base of tongue cancer (BOTSCC), together accounting for 80-90% of all OPSCCs, and mainly affecting men. The epidemic was later revealed to be due to a rise in HPV-positive cases, and scientists in the field suggested HPV vaccination also of boys. Globally, there are roughly 96 000 incident OPSCC cases/year of which 20-24% are caused by HPV, thereby accounting for around 22 000 OPSCC cases annually. Of these cases, 80-90% are due to HPV16 infection and would be prevented with the presently registered HPV vaccines. In Western countries, such as Sweden (with almost 400 TSCC and BOTSCC cases per year) and the United States, HPV prevalence in OPSCC is higher and around 70%. HPV vaccination of girls has been initiated in many countries, and the vaccines have been efficient and their side effects limited. HPV vaccination of boys has, however, been the exception, but should definitely not be delayed any further. It would benefit both girls and boys directly, and result in better and more robust herd immunity. Today, we have the possibility to eliminate several high-risk HPV types in the younger generations and avoid more than 600 000 cancer cases annually worldwide, and this possibility should be embraced by offering global pan-gender HPV vaccination.

Diverging incidence trends for larynx and tonsil cancer in low socioeconomic regions of the US.

OBJECTIVE: Oropharynx cancer incidence trends in low socioeconomic (SES) regions of the United States (US) have not been well described. Our objective was to describe tonsil cancer incidence trends in low SES regions, and compare observed trends with those for larynx cancer. MATERIALS AND METHODS: Age-adjusted incidence rates and trends for tonsil and larynx squamous cell carcinomas (2000-14) from Surveillance, Epidemiology, and End Results (SEER 18) were evaluated using SEER*Stat and Joinpoint 4.5.0.1. Annual percentage changes (APCs) were compared between low and high SES counties. The laryngeal cancer cohort was included as a comparator reflecting a tobacco-related malignancy. RESULTS: Tonsil cancer incidence trends increased at least as much in low SES as in high SES counties (APC/AAPC 4.4, 95%CI 2.4-6.4 versus APC/AAPC 2.9, 95%CI 2.4-3.3). Pairwise comparison confirmed no differences between incidence trends across SES quintiles for tonsil cancer incidence rates. In contrast, age-adjusted incidence rates of larynx cancer decreased in high SES counties (APC/AAPC -2.4, 95%CI -2.4 to -2.0, p < 0.001) and were stable in low SES counties (APC/AAPC -0.9, 95%CI -1.9 to 0.2, p = 0.10). Compared with larynx cancer patients, tonsil cancer patients in low SES regions were significantly more likely to be younger and white. CONCLUSION: In low SES US counties, tonsil cancer incidence rates increased from 2000 to 2014, while larynx cancer rates did not change, reflecting diverging trends for larynx and tonsil cancers. Tonsil cancer incidence rates are increasing in most US regions regardless of regional socioeconomic status. Prevention efforts should take these findings into account.

Incidence of indications for tonsillectomy and frequency of evidence-based surgery: a 12-year retrospective cohort study of primary care electronic records.

BACKGROUND: Neither the incidence of indications for childhood tonsillectomy nor the proportion of tonsillectomies that are evidence-based is known. AIM: To determine the incidence of indications for tonsillectomy in UK children, and the proportion of tonsillectomies meeting evidence-based criteria. DESIGN AND SETTING: A retrospective cohort study of electronic medical records of children aged 0-15 years registered with 739 UK general practices contributing to a research database. METHOD: Children with recorded indications for tonsillectomy were identified from electronic medical records. Evidence-based indications included documented sore throats of sufficient frequency and severity (Paradise criteria); periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA); or tonsillar tumour. Other indications were considered non-evidence-based. The numbers of children subsequently undergoing tonsillectomy was then identified. The numbers with evidence-based and non-evidence-based indications for surgery among children who had undergone tonsillectomy were determined. RESULTS: The authors included 1 630 807 children followed up for 7 200 159 person-years between 2005 and 2016. Incidence of evidence-based indications for tonsillectomy was 4.2 per 1000 person years; 13.6% (2144/15 760) underwent tonsillectomy. Incidence of childhood tonsillectomy was 2.5 per 1000 person years; 11.7% (2144/18 281) had evidence-based indications, almost all with Paradise criteria. The proportion of evidence-based tonsillectomies was unchanged over 12 years. Most childhood tonsillectomies followed non-evidence-based indications: five to six sore throats (12.4%) in 1 year, two to four sore throats (44.6%) in 1 year, sleep disordered breathing (12.3%), or obstructive sleep apnoea (3.9%). CONCLUSION: In the UK, few children with evidence-based indications undergo tonsillectomy and seven in eight of those who do (32 500 of 37 000 annually) are unlikely to benefit.

Occult malignancy in pediatric tonsil and adenoid surgeries - A national survey.

OBJECTIVE: To evaluate the incidence of tonsil and adenoid malignancy in pediatric patients in Israel compared to the known literature and to revisit the common practice of routine histopathologic examination of tonsils and adenoids. METHODS: Analysis of the Israel National Cancer Registry data on pediatric tonsil and adenoid malignancies between the years 2005 and 2015, and a systematic literature review of all relevant articles that reported on malignancies amongst pediatric patients who underwent tonsillectomy with or without adenoidectomy. RESULTS: Only seven cases of tonsillar malignancies were documented out of 152,352 (0.0052%) surgeries in the pediatric population. All malignancies were lymphoproliferative and mainly Burkitt's lymphoma. In our medical center no malignancy was found in 2165 patients in the same age groups and time period. We found the incidence of tonsillar malignancy in Israel to be significantly lower (p = 0.013) compared to the previously described literature. CONCLUSION: The incidence of malignancy in routine histopathological examination of tonsils and adenoids is Israel is very low when compared to the known literature. According to these results, we suggest that routine histopathological examination of all such samples is not clinically justified.

Changes in incidence and prevalence of human papillomavirus in tonsillar and base of tongue cancer during 2000-2016 in the Stockholm region and Sweden.

BACKGROUND: Tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) has increased. In Stockholm, the proportion of human papillomavirus (HPV)-positive cases and the incidence of TSCC rose between 1970 and 2006 then stabilized. Here, HPV-prevalence, and TSCC/BOTSCC incidence 2000-2016, in Stockholm and Sweden were followed. METHODS: Incidence data for 2000-2016 were obtained from the Swedish Cancer Registry. TSCC/BOTSCC biopsies, 2013-2016 from Stockholm, were examined for HPV DNA and p16INK4a , or data obtained from medical reports. For cases 2000-2012, data were available from previous studies. RESULTS: The incidence of TSCC/BOTSCC has continued to rise in Stockholm and Sweden 2000-2016, especially after 2008. HPV DNA and p16INK4a analysis was determined for 795 Stockholm cases from 2000 to 2016, with 72% being HPV DNA and p16INK4a positive 2013-2016, and 70% positive 2000-2016. CONCLUSION: During 2000-2016, especially after 2008, the incidence of TSCC/BOTSCC has continued to increase in Stockholm and Sweden, with an HPV-prevalence of approximately 70% in Stockholm.

Pediatric Tonsil Cancer: A National and Institutional Perspective.

OBJECTIVE: To evaluate childhood and adolescent tonsil cancer incidence and to identify the clinical characteristics indicative of those patients who would benefit from urgent operative intervention. STUDY DESIGN: The Surveillance, Epidemiology and End Results 18 database, inclusive of national cancer statistics from 1973 to 2013, provided quantitative tonsil cancer incidence data. An institutional retrospective chart review of pediatric patients diagnosed with tonsil malignancy from January 2013 to January 2017 identified supplementary qualitative clinical presentation information. RESULTS: The Surveillance, Epidemiology and End Results 18 database included 138 pediatric patients with tonsil cancer with an age-adjusted incidence rate of 0.021/100 000 patients per year. The majority of cases were unilateral (79.7%), and there was both a male and Caucasian predominance. Non-Hodgkin lymphoma (84.1%) was the most common malignancy, of which Burkitt lymphoma (31.1%), diffuse large B-cell lymphoma (26.8%), and follicular lymphoma (10.1%) were the most common subtypes. Five tonsillar malignancy patients were identified upon institutional chart review. The majority likewise had non-Hodgkin lymphoma and all shared a history of rapid tonsillar enlargement over ≤12 weeks. Significant tonsillar asymmetry was present in 4 patients. Four patients additionally exhibited prominent cervical lymphadenopathy. CONCLUSIONS: Pediatric tonsil cancer is rare, with non-Hodgkin lymphoma accounting for the majority of pediatric tonsillar malignancies. A high index of suspicion is appropriate in children who present with relatively rapid tonsil enlargement, tonsillar asymmetry characterized by a difference in tonsillar size of ≥2 degrees on the Brodsky scale, or concurrent prominent cervical lymphadenopathy.

Prevalence of synchronous bilateral tonsil squamous cell carcinoma: A retrospective study.

OBJECTIVES: The prevalence of synchronous bilateral tonsil cancer remains unexplored. To date, only 38 cases have been described in the literature. With an aim to substantiate the Danish recommendation of performing bilateral tonsillectomy in patients with suspected or proven tonsil cancer and in patients with cervical carcinoma metastasis from an unknown primary tumour, this study was undertaken to determine the prevalence of synchronous bilateral tonsil cancer. DESIGN: A retrospective review of all patients diagnosed with tonsil cancer in the period 2000-2015, Aarhus University Hospital, Denmark, was performed. RESULTS: Seven of 211 (3.3%) consecutive patients with tonsil cancer, who had undergone bilateral tonsillectomy (n = 180) or unilateral tonsillectomy (clinically normal side) combined with contralateral tonsil biopsy (side with suspected cancer) (n = 31), had synchronous bilateral tonsil cancer. Furthermore, dysplasia was found in the contralateral tonsil in two patients with unilateral tonsil cancer. Four of 171 (2.3%) patients with suspected unilateral tonsillar cancer had additional contralateral tonsil cancer. Three of 34 (8.8%) patients without clinical signs of tonsillar malignancy on any side (32 patients with carcinoma of unknown primary) had synchronous bilateral tonsil cancer. In none of the patients were bilateral tonsil cancer suspected. Patients with unilateral vs synchronous bilateral tonsil cancer had similar clinical and tumour characteristics. CONCLUSION: Knowledge on additional contralateral synchronous tonsil cancer is crucial for avoidance of early recurrence of oropharyngeal cancer in patients with tonsil cancer. Based on our findings, we recommend bilateral tonsillectomy in all patients with suspected or proven tonsil cancer and carcinoma of unknown primary.

Human polyomavirus and human papillomavirus prevalence and viral load in non-malignant tonsillar tissue and tonsillar carcinoma.

Human papillomaviruses (HPVs) are an acknowledged cause of a subset of oropharyngeal cancers, especially of tonsillar cancer. Similar to HPV, some human polyomaviruses (HPyVs), such as Merkel cell polyomavirus (MCPyV), have an oncogenic potential. Recently, several novel HPyVs have been discovered. The aim of our study was to determine viral DNA prevalence and viral DNA load of 13 different HPyVs in benign and malignant tonsillar tissue and to compare the data with those found for HPV. A total of 78 biopsies of palatine tonsils with a histologic diagnosis of non-malignant disease (chronic tonsillitis, tonsillar hyperplasia, n = 40) or tonsillar squamous cell carcinoma (n = 38) were included in the study. HPyV DNA prevalence and viral load were determined by virus-specific quantitative real-time PCRs. JCPyV (1/40, 2.5%) and WUPyV (3/40, 7.5%) were only found in non-malignant tonsillar tissue. HPyV7 and HPyV10 were only detected in one (2.6%) and seven (18.4%) of the 38 cancer biopsies, respectively. Both MCPyV (8/38, 21.1 vs. 4/40, 10.0%) and HPyV6 (2/38, 5.3 vs. 1/40, 2.5%) were found more frequently in cancer samples than in non-malignant tissue, but the differences were not significant. BKPyV, KIPyV, TSPyV, HPyV9, STLPyV, HPyV12 and NJPyV were not discovered in any of the samples. HPyV loads found in HPyV DNA-positive biopsies were very low with no difference between non-malignant and malignant samples (median load <0.0001 HPyV DNA copies per beta-globin gene copy, respectively). In contrast to HPyV, high-risk HPV types (HPV16/HPV18) were found significantly more frequently in tonsillar cancers than in non-malignant tonsillar tissue (17/38, 44.7 vs. 2/40, 5.0%, p < 0.001). Furthermore, high-risk HPV DNA loads were significantly higher in the cancer compared to the non-malignant samples (median load 11.861 vs. 7 × 10-6 HPV DNA copies per beta-globin gene copy, p = 0.012). While both HPV and HPyV may persist in tonsillar tissue, our data on HPyV DNA prevalence and load do not support a role of HPyV in tonsillar carcinogenesis, neither alone nor as co-infecting agents of HPV.