Human papillomavirus and head and neck squamous cell carcinoma in a UK population: Is there an association?

Background: Human papillomavirus (HPV) is an evolving important risk factor for head and neck cancer (HNC), especially for individuals who do not smoke and drink alcohol. The aim of this study was to establish the prevalence of HPV infection and elucidate its association with head and neck squamous cell carcinoma (HNSCC) patients in UK population. Methods: The presence and association of HPV was investigated in HNSCC patients in this retrospective clinical study. Samples were obtained from archived biopsies and resections. HPV screening was performed by the use of polymerase chain reaction (PCR) using the GP5+/GP6+ and the SPF1/2 consensus as primers and by immunohistochemistry (IHC). Samples of viral warts that were IHC positive for HPV and fibroepethelial polyps (FEP) were used, as positive and negative controls, respectively. Results: The cohort included 124 patients with HNSCC with an age range of 27-97 years (median, 60 years) and a male to female ratio of 2:1. Among the 124 HNSCC, 43/124 (34.7%) were from the tongue, 74/124 (60%) presented with advanced stage III or IV disease, 112/124 (90%) had a conventional phenotype, 84/124 (68%) were moderately differentiated, and 89/124 (72%) had bands or cords at the invasive front. Of the 124 patients with HNSCC, 84/124 (68%) demonstrated the presence of HPV, 0/124 (0%) was for oral squamous cell carcinomas (OSCC). HPV16 was the associated virus type in all positive samples. However, no significant association was observed between HPV positivity and other clinico-pathological variables including age and gender of the patients, stage, and malignancy differentiation. Conclusion: The results we provide suggest that HPV infection is low in HNSCC, in general, and absent in OSCC, specifically, in this UK population during this time period. This implies that HPV infection may not play an important role in HNSCC carcinogenesis compared to other risk factors in UK population. This information can aid in more effective treatment approaches for treating UK cases of HNSCC.

Merkel cell carcinoma of the head and neck in the south-east of England.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy of the skin. Its incidence is increasing with half of cases involving the head and neck. To the best of our knowledge, few large studies have been published in the UK, and to date this is the largest reported series of head and neck MCC. We retrospectively reviewed the outcomes of patients with MCC in three hospitals in the south-east of England over a 12-year period (2008-2019). Diagnosis was based on histological data following biopsy. Overall survival and disease-specific survival were calculated using Kaplan-Meier and log-rank tests. Fifty-eight patients met the inclusion criteria (24 stage I, 22 stage II, 9 stage III, and 3 unclassified). Median disease-free survival was 36 months (95% CI 0 to 77.2) and median overall survival 50 months (95% CI 29.9 to 70). Overall five-year survival was 34.4% (95% CI 17% to 52%) with two-year survival at 62% (95% CI 48% to 76%). Five-year disease-free survival was 26.7% (95% CI 17 to 52%) with two-year disease-free survival at 54% (95% CI 40% to 68%). To date, this is the largest UK based study reporting overall and disease-free survival associated with MCC of the head and neck. Half the patients presented late, and surgery was the mainstay of treatment, augmented by adjuvant radiotherapy. There is a need to better stratify patients at risk of developing metastatic disease, with the use of sentinel lymph node biopsy and positron-emission tomography-computed tomography (PET-CT), as immunotherapy and targeted agents are now available to treat advanced disease.

Challenges and outcomes in establishing a sentinel lymph node biopsy service for oral squamous cell carcinoma in a regional district specialist hospital.

UK national guidelines in 2016 recommended that sentinel lymph node biopsy (SLNB) should be offered to patients with early oral squamous cell carcinoma (OSCC). We review the establishment of an OSCC SLNB service with specific consideration to resources, service implications and patient outcomes. A review of processes was performed to identify key stages in establishing the service, and subsequently a retrospective cohort study consisting of 46 consecutive patients with T1/T2 N0 OSCC was undertaken. The key stages identified were: coordinating a nuclear medicine pathway and reliable cost-appropriate pathology service, constructing a Trust business case, and gaining approval of a new interventional service policy. A median (range) of 3.3 (1-8) sentinel nodes (SLN) were removed, with 17 patients having a positive SLN. The negative predictive value of SLNB was 100%, with 12 having a SLN outside the field if elective neck dissection (END) was planned. There was a significantly increased risk of a positive SLN with increasing depth of invasion (DOI) (p=0.007) and increased diameter (p=0.036). We also identified a longer-than-ideal time to completion neck dissection and inadequate ultrasound follow up of negative SLNB patients. Establishment of a service requires careful planning. Our results were in keeping with those reported in the literature, and showed that SLNB for OSCC has a high negative predictive value and can identify at-risk SLN outside the traditional END levels, even in well-lateralised tumours. Our findings show that DOI and size of SLN were significantly associated with a positive SLN, and also identified areas requiring improvement.

Patients undergoing primary surgery for oral and oropharyngeal cancer: how many are referred on the two-week wait pathway and by whom?

INTRODUCTION: Available data suggest that the two-week wait referral pathway is ineffective at expediting diagnosis of cancer due to large numbers of inappropriate referrals. This study aimed to compare the referral pathway of 125 patients who had undergone primary surgery for oral and oropharyngeal cancer with 100 who had been two-week wait referrals. MATERIALS AND METHODS: This was a case note review. RESULTS: Of the 125 patients who underwent surgery; 47 (38%) were referred via the 2WW pathway. GPs had referred 25 (53%) of the 47 patients and general dental practitioners 22 (47%). The tumour stage was similar regardless of referral pathway (two-week wait or routine). GPs recognised that the two-week wait pathway was needed in 49% of the patients they had referred, whereas the equivalent figure for GDPs was 40%. Of the 100 2WW patients, 52 were biopsied. Of these, nine (9%) were diagnosed with a malignancy. GPs referred 61% of the 100 two-week wait patients and accurately diagnosed five of the cancers (although two were basal cell carcinomas), general dental practitioners the remainder (including one basal cell carcinoma). Overall, 41% of the patients referred on the two-week wait pathway by GPs needed a biopsy, compared with 69% of those referred by general dental practitioners. CONCLUSIONS: While the criteria for referral on the two-week wait pathway lack discrimination and the majority of referrals proved benign, nearly 40% of surgically treated patients were referred via this pathway, suggesting that it does serve a useful purpose. More patients with cancer were referred by GPs, but more two-week wait referrals by general dental practitioners warranted biopsy.

Verruciform Xanthoma of the Oral Mucosa: A Series of Eight Typical and Three Anomalous Cases.

In this series, there are 8 typical verruciform xanthomas of the oral mucosa and 3 anomalies, 1 polypoid, 1 florid, and 1 carcinomatous. All were characterized by infiltrates of CD68-positive xanthomatous histiocytes in the lamina propria. The 11 patients comprised 6 men and 5 women (mean age = 54.5 years, range = 40-69). Both keratinized and nonkeratinized sites were affected. A history of lichenoid inflammation was recorded in 5 patients. The polypoid xanthoma presented in a woman aged 54 years as a polyp of the labial commissure. The florid lesion affected the dorsum of the tongue of a man aged 54 years and at 20 mm was the largest of the 11 lesions, but the only one with candidal infection. The squamous cell carcinoma manifested as a papilloverrucous hyperkeratosis of the palatal gingiva in a man aged 69 years. The latter 2 (and 1 "typical" verruciform xanthoma) required re-excision, but none has since recurred.

Staging of squamous cell carcinoma of the tongue: extrinsic lingual muscles and the 8th editions of the American Joint Committee on Cancer/Union for International Cancer Control staging manuals.

Our aim was to find out first whether the extrinsic muscles of the tongue are histologically identifiable, and secondly to what degree the use of the new criteria in the 8th editions of the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control (UICC) manuals (which have recognised the importance of depth of invasion of tumour, rather than invasion of the extrinsic muscles of the tongue and extranodal extension), will alter staging of lingual squamous cell carcinoma (SCC). The histological sections from 165 patients who had had primary resection of lingual SCC were reviewed, and one or more extrinsic muscles of the tongue was identified in 100 patients (61%), with the genioglossus seen the most often (in 96). By contrast, the hyoglossus was identified in only eight patients, the styloglossus in two, and the palatoglossus in none. Identification was straightforward only in extensive resections. Applying the criteria from the 8th edition increased the number of pT3 SCC with a simultaneous reduction in pT4a tumours. The number of pN2b SCC was also reduced, but the new category of pN3b meant that overall 53% of tumours were upstaged. The kappa scores for agreement between the two sets of criteria were 0.221 (weighted 0.410) for the pT values, 0.508 (0.713) for pN values (but 0.227, weighted 0.386, if the pN0 values were removed before calculation), and 0.243 (0.514) for overall stage, indicating poor to fair agreement. We conclude that the removal of invasion of extrinsic muscles of the tongue as a criterion for a pT4a SCC is justified, and that many SCC of the tongue will be upstaged as a result of implementation of the 8th editions.

Solitary fibrous tumour of the tongue: a series of four cases.

BACKGROUND: Solitary fibrous tumour is a soft tissue tumour of mesenchymal origin. It was first described in the pleura and has since been reported in many anatomical locations. Thirteen cases in the tongue have hitherto been reported. A positive CD34 result has traditionally been used to confirm the diagnosis, although this is often non-specific to solitary fibrous tumour. To date, nuclear STAT6 expression has not been reported in solitary fibrous tumour of the tongue. METHOD: This paper presents a further four cases of solitary fibrous tumour of the tongue, the largest series to date. Clinical, histopathological and immunohistochemical findings are detailed, including nuclear STAT6 expression. RESULTS: All four cases were positive for CD34; two cases showed nuclear expression of STAT6. The tumours were excised completely and there have been no recurrences in at least one year. CONCLUSION: Solitary fibrous tumour should be considered as a differential diagnosis for tongue swellings, with the potential to recur.

Compliance of referral and hospital documentation with National Institute of Health and Care Excellence guidelines for the extraction of third molars: a comparative analysis of two NHS Trusts.

To find out whether documentation for the extraction of wisdom teeth complies with National Institute of Health and Care Excellence (NICE) guidelines, we reviewed the referral letters and hospital notes of patients treated at the maxillofacial unit of two NHS Trusts (A: 314 records and B: 280) over 12 months (1 September 2012 to 31 August 2013). Compliance was assessed as unsatisfactory ("indication for extraction not mentioned", "incorrect indication", "indication unclear") or satisfactory ("correct indication implied", "correct indication explicit"). The grade of the clinician who examined the patient was also recorded. A total of 194/314 (62%) referral letters in Trust A and 126/280 (45%) in Trust B were unsatisfactory (p<0.001). Hospital notes were unsatisfactory in 168/323 (52%) and 87/297 (29%) of cases, respectively (p<0.001). In Trust A, middle grades saw 23% (75/323) of the patients, as compared with 53% (157/297) in Trust B. In both, junior staff produced the highest percentage of satisfactory documentation, but in Trust A they were also responsible for most of the unsatisfactory examples. However, senior house officers saw 60% (195/323) of the patients in Trust A, and only 28% (83/297) in Trust B. Consultants were responsible for significantly more unsatisfactory documentation (p<0.001). One referral letter (0.2%) and seven hospital records (1%) explicitly and accurately complied with the guidelines. We conclude that compliance of documentation with the current NICE guidelines is poor and inconsistent.

Inflammatory pseudotumour of the maxilla.

Inflammatory pseudotumour (IP), also known as inflammatory myofibroblastic tumour (IMT), is a rare lesion of the maxillofacial skeleton and a diagnosis by exclusion. We describe three cases which affected the maxilla, two women and one man of ages 67, 56 and 70 years at presentation. All showed the typical, rather non-specific histopathological features. IgG4-positive plasma cells varied greatly in prominence, and none of the three lesions expressed ALK-1. Both women responded to steroids and radiotherapy, though one also required azathioprine. Despite maxillectomy, radiotherapy, steroids and cyclophosphamide, the man suffered intracranial spread and succumbed to persistent disease. The cases described here demonstrate the clinicopathological difficulties presented by this entity and its aggressive, unpredictable behaviour.

Persistent Ehrlichia ewingii infection in dogs after natural tick infestation.

BACKGROUND: Ehrlichia ewingii, which causes disease in dogs and people, is the most common Ehrlichia spp. infecting dogs in the United States, but little is known about how long E. ewingii infection persists in dogs. HYPOTHESIS/OBJECTIVES: To evaluate the persistence of natural infection with E. ewingii in dogs. ANIMALS: Four Class A Beagles; no previous exposure to ticks or tick-borne infectious agents. METHODS: Dogs were exposed to ticks by weekly walks through tick habitat in north central Oklahoma; dogs positive for infection with Ehrlichia spp. by sequence-confirmed PCR and peptide-specific serology were evaluated for 733 days (D). Whole blood was collected once weekly for PCR, and serum was collected once monthly for detection of antibodies to Ehrlichia canis (peptide p16), Ehrlichia chaffeensis (indirect fluorescence antibody [IFA] and variable-length PCR target [VLPT]), and E. ewingii (peptide p28). RESULTS: All dogs (4/4) became infected with Ehrlichia spp. as evidenced by seroconversion on IFA to E. chaffeensis (4/4); PCR detection of E. ewingii (4/4) and E. chaffeensis (2/4) DNA using both nested and real-time assays; and presence of specific antibodies to E. ewingii (4/4) and E. chaffeensis (2/4). Infection with E. chaffeensis was not detected after D55. Intermittent E. ewingii rickettsemia persisted in 3 of 4 dogs for as long as 733 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Our data demonstrate that dogs infected with E. ewingii from tick feeding are capable of maintaining infection with this pathogen long-term, and may serve as a reservoir host for the maintenance of E. ewingii in nature.

Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) in squamous cell carcinoma of the tongue: markers of nerve invasion?

PURPOSE: Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is an independent predictor of poor prognosis. As PNI is not always identified with routine histology, a surrogate marker of PNI would improve detection and better inform treatment planning. The chemokines fractalkine (CX3CL1) and its receptor (CX3CR1) have shown such potential in other cancers, but have yet to be investigated with respect to PNI in oral SCC. METHODS: Thirty SCCs of the tongue in which PNI was identified histologically, and 30 in which it was not, were stained for fractalkine and fractalkine receptor using polyclonal antibodies and an immunoperoxidase technique. Tumours were assessed as either positive or negative; no attempt was made to subjectively assess staining intensity or extent. RESULTS: Both markers labelled myofibroblasts in the stroma surrounding the tumour, various neural components, leucocytes, endothelium and salivary myoepithelial cells. Fractalkine also labelled salivary ductal epithelium, vascular smooth muscle and 12/30 SCC which showed PNI. Eight of 30 positive SCCs in which PNI was not identified were also positive for this marker. There was no statistically significant association between fractalkine staining and PNI (p = 0.273). No SCC was positive for fractalkine receptor, but immune dendritic cells within tumour islands were strongly positive, as was striated muscle. CONCLUSIONS: Neither fractalkine nor fractalkine receptor is a reliable surrogate marker of PNI in lingual SCC.

Basal cell carcinoma metastatic to parotid gland.

Metastasis from basal cell carcinoma of the skin is very rare with cases being documented in the lymph nodes, lung, bone and parotid gland. The main histopathological differential diagnosis is the locally arising basal cell adenocarcinoma from which it is difficult to distinguish by morphology and routine immunohistochemistry. Approximately 85 % of all reported metastatic basal cell carcinomas arise in the head and neck region. Here we present a case of basal cell carcinoma of the skin of the left lateral canthus of the eye which metastasized to the intraparotid lymph nodes with infiltration of the adjacent parotid parenchyma. More awareness and vigilance is required on the part of the reporting pathologist to consider metastasis in the presence of a parotid tumour. Features favouring metastasis include history of primary cutaneous basal cell carcinoma, histological similarity to the primary lesion and absence of any demonstrable direct extension from the skin lesion. We also review the literature on metastatic basal cell carcinoma and discuss the need for adequate follow up in high risk patients.

Essential mixed cryoglobulinemia manifesting as recurrent perioral edema: report of a case.

Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures <37°C but that redissolve if heated; they are broadly divided into 3 classes. Cryoglobulinemia has a plethora of clinical manifestations, but it typically presents a vasculitic syndrome, most notably a triad of purpura, arthralgia, and weakness secondary to cryoglobulin deposition in small or medium-sized blood vessels. The highly variable clinical presentation and inconsistent laboratory isolation of cryoglobulins mean that the diagnosis may be one of exclusion or of retrospective review. We describe a case of a 67-year-old woman whose principal symptom was recurrent perioral edema, which was characteristically induced by cold. Raised cryoglobulins combined with a positive autoantibody screen suggested mixed cryoglobulinemia secondary to Sjögren syndrome. However, in the subsequent 6 years, she has remained generally well, having developed no autoimmune, neoplastic, or other disease, suggesting the diagnosis is one of "essential" mixed cryoglobulinemia. No treatment other than symptomatic analgesia has been required.

Chondroid lipoma of the tongue: a report of two cases.

BACKGROUND: Chondroid lipoma affecting the oral cavity is rare and usually presents as a polyp of benign clinical appearance which is easily excised. However, the histopathological features of chondroid lipoma resemble liposarcoma due to the presence of lipoblasts and lack of mature cartilage. CASE REPORTS: The clinicopathological features of two cases of chondroid lipoma of the dorsum of the tongue, one in a 66-year-old woman and the other in a 43-year-old man, are described. CONCLUSION: Once the diagnosis had been established, no treatment other than surgical excision was necessary and in neither case has there been recurrence in two years of follow-up.

Bilateral asynchronous renal cell carcinoma with metastatic involvement of the tongue.

Renal cell carcinoma (RCC) has a propensity for distant organ metastasis and late recurrence, involving not only the ipsilateral but also contralateral kidney. Lingual metastasis by RCC is rare. We present an unusual case of bilateral asynchronous RCC. Involvement of the right kidney was discovered only after a metastatic tongue lesion was diagnosed. The original RCC had been treated by left nephrectomy 14 years previously. Due to end-stage primary pulmonary malignancy, and poor function of the remaining kidney, immunotherapy was unsuitable. Palliative local resection of the lingual metastasis alleviated functional difficulties and was preventative against airway obstruction, but the patient died five months later.