Significant variation in human papillomavirus (HPV) prevalence in oropharyngeal squamous cell carcinoma (OPSCC) across countries ranging from 11% in Brazil to 74% in New Zealand has been reported earlier. The aim of this study was to systematically review the most recently published studies on the occurrence of HPV in OPSCC globally. PubMed and Embase were systematically searched for articles assessing the occurrence of HPV+ OPSCC published between January 2016 and May 2021. Studies with a study period including 2015 and the following years were included. Both HPV DNA and/or p16 were accepted as indicators of HPV+ OPSCC. 31 studies were enrolled comprising 49,564 patients with OPSCC (range 12–42,024 patients per study) from 26 different countries covering all continents. The lowest occurrences of HPV+ OPSCC were observed in India (0%) and Spain (10%) and the highest occurrences were observed in Lebanon (85%) and Sweden (70%). We observed great variation in HPV prevalence in OPSCC worldwide varying from 0% to 85%. The highest occurrences of HPV+ OPSCC were found in general in Northern European countries, USA, Lebanon, China, and South Korea. We observed a trend of increase in HPV-positivity, indicating a mounting burden of HPV+ OPSCC.

Focal epithelial hyperplasia (FEH) or Heck’s disease is a rare, benign, oral condition that is associated with infection by human papillomavirus type 13, 32 or both. The whiteish to mucosal-colored, soft, papular or nodular elevated lesions in the oral cavity are normally asymptomatic but can grow to a size or at a location where treatment is needed. The diagnosis is often based on clinical presentation and histopathology, and the HPV genotype can be determined using PCR utilizing specific primers or DNA sequencing. While FEH was reported to often affect several members of the same family and exist primarily among indigenous populations around the world, the number of reported cases within the European region is increasing. This contemporary review summarizes the main findings in relation to HPV genotypes, impact of superinfection exclusion and vaccination, transmission, diagnosis, geographical and ethnical distribution, comorbidities and treatment of FEH with an emphasis on including the most recent case reports within the field. Furthermore, we describe for the first time a FEH lesion infected with the low-risk HPV90.

Purpose: No effective treatment exists for radiation-induced xerostomia. The objective of this study was to compare the effect of adipose-derived mesenchymal stem/stromal cell (ASC) injection, relative to placebo, on salivary gland function in patients with radiation-induced xerostomia. Patient and Methods: In this single-centre, double-blind, placebo-controlled trial, patients with hyposalivation were randomised to receive ultrasound-guided injections of allogeneic ASCs or placebo into the submandibular glands. Patients were followed for 4 months. We evaluated unstimulated whole salivary flow rate (UWS), stimulated salivary flow rate, and patient-reported outcomes. Adverse events were recorded and immune response determined in blood samples. Results: We enrolled 120 patients. ASC treatment resulted in a statistically significant UWS increase of 0.04 [95% confidence interval (CI), 0.02–0.06] mL/min (38%) compared with pretreatment baseline whereas placebo treatment did not cause a significant increase [0.01 (95% CI, −0.01 to 0.04) mL/min (21%)]. Both the ASC and placebo treatment yielded notable symptom reductions, with dry mouth decreasing by 13.6 and 7.7 units, sticky saliva decreased by 14.8 and 9.3 units, swallowing difficulties decreased by 7.9 and 8.0 units, and the summary score of the Xerostomia Questionnaire decreased 5.9 and 5.1 units for the ASC and placebo arms, respectively. We found no statistically significant group difference between the ASC and placebo arms for any of the outcomes. Conclusions: We could not confirm superiority of the ASC relative to placebo. ASC therapy significantly improved UWS in previous patients with head and neck cancer, whereas placebo resulted in an insignificant increase.

Second primary cancer (SPC) is the second most common cause of death among patients diagnosed with head and neck cancer. This study examined the risk of SPC following oropharyngeal squamous cell carcinoma (OPSCC) and the impact of human papillomavirus (HPV) on survival following SPC. The study was a population-based, retrospective study including all patients diagnosed with OPSCC in eastern Denmark from 2000–2020 who received curative intended treatment. The incidence rate ratio (IRR), age-adjusted incidence rates (AAIR), and hazard ratios (HR) were calculated. A total of 2584 patients with primary OPSCC were included (median follow-up time: 3.1 years), with 317 patients (12.3%) diagnosed with SPC. The risk of SPC was approximately five times the occurrence of cancer in the general population (IRR: 4.96). The median time to SPC after a primary OPSCC was 2.0 years (interquartile range (IQR) = 0.6–4.2 years). HPV-positive (HPV+) patients had a significantly longer median time to SPC, and a significant better survival compared to HPV-negative (HPV-) patients. SPC was most frequently found in lungs, head, and neck (LHN) for HPV- OPSCC patients and lungs followed by gender-specific (prostate, ovaries, or endometrium) for HPV+ OPSCC. There was a significant difference between the two groups when distributed between “within” or “outside” LHN. Patients with SPC outside LHN had a significant better overall survival. This knowledge should be considered during post-treatment surveillance and might guide targeted imaging.

Background: Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies. Methods: PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO (www.crd.ac.uk/prospero), registration number CRD42021227336. Results: A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55–11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors. Conclusion: In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting. Graphical

Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV). There were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002). We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.