Does HPV vaccination initiation at age 9, improve HPV initiation and vaccine series completion rates by age 13?

Vaccination for Human Papillomavirus (HPV) is important to reduce rates of cervical and oropharyngeal cancer. We aimed to evaluate if a program to initiate HPV vaccination at 9 years improved initiation and completion rates by 13 years of age. Data on empaneled patients aged 9-13 years from January 1, 2021 to August 30, 2022 were abstracted from the electronic health record. Primary outcome measures included HPV vaccination initiation and series completion by 13 years of age. The secondary outcome measure was missed opportunities for HPV vaccination. In total, 25,888 patients were included (12,433 pre-intervention, and 13,455 post-intervention). The percentage of patients aged 9-13 with an in-person visit who received at least 1 dose of HPV vaccine increased from 30% pre-intervention to 43% post-intervention. The percentage of patients who received 2 doses of vaccine increased from 19.3% pre-intervention to 42.7% post-intervention. For the overall population seen in-person, initiation of HPV vaccination by age 13 years increased from 42% to 54%. HPV completion increased as well (13% to 18%). HPV vaccination initiation at 9 years of age may be an acceptable and effective approach to improving vaccination rates.

Circulating tumor HPV DNA as an alternative method to determine HPV status in oropharyngeal squamous cell carcinoma.

Human Papilloma Virus (HPV) testing is mandatory for all newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) due to its importance for prognostication and aiding in treatment decision making. Fine needle aspiration (FNA) is a widely used and accepted diagnostic tool for OPSCC. Although FNA can accurately determine histological diagnosis, results are often indeterminate or lack insufficient samples for HPV testing. For samples with an indeterminant FNA, we propose an alternate method for determining HPV status using circulating tumor tissue modified HPV DNA (ctHPVDNA). We report three cases that confirmed HPV status using ctHPVDNA following an indeterminate FNA. If validated, this non-invasive assay could prevent the need for repeat FNAs or operative biopsies for the sole purpose of determining HPV status.

Prognostic Role of Porphyromonas gingivalis Gingipain Rgp and Matrix Metalloproteinase 9 in Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: The oral bacteria involved in the development of periodontitis alter the tissue conditions and modify immune responses in a way that may also influence tumor development. We investigated the prevalence of R gingipain (Rgp), a key virulence factor of the oral pathobiont Porphyromonas gingivalis, and the tissue-destructive enzymes matrix metalloproteinase 8 (MMP-8) and 9 (MMP-9) in 202 unselected consecutive oropharyngeal squamous cell carcinoma (OPSCC) samples. We further investigated the relationships between these factors and human papillomavirus (HPV) status, Treponema denticola chymotrypsin-like proteinase (Td-CTLP) immunoexpression, clinical parameters, and patient outcome. PATIENTS AND METHODS: Clinicopathological data were derived from university hospital records. Rgp, MMP-8, and MMP-9 immunoexpression was evaluated by immunohistochemistry; the immunohistochemistry of Td-CTLP and HPV has been described earlier for this patient series. Cox regression analysis including death by causes other than OPSCC as a competing risk served to assess sub distribution hazard ratios. RESULTS: In multivariable survival analysis, positive tumoral MMP-9 immunoexpression predicted poor prognosis among all patients [sub distribution hazard ratio (SHR)=2.4; confidence interval (CI)=1.2-4.4, p=0.008], and especially among those with HPV-negative OPSCC (SHR=3.5; CI=1.7-7.3, p=0.001). Positive immunoexpression of Rgp in inflammatory cells was associated with favorable outcome among all patients (SHR=0.5, CI=0.2-0.9, p=0.021) and among those with HPV-negative disease (SHR=0.4, CI=0.2-0.9, p=0.022). CONCLUSION: Our results suggest that tumoral MMP-9 may be related to poor outcome in OPSCC, especially in HPV-negative disease, while Rgp immunoexpression in inflammatory cells is associated here with better disease-specific survival (DSS).

The collateral impact of the COVID-19 pandemic on HPV-positive oropharyngeal cancer diagnosis.

PURPOSE: We aim to assess the potential impact of the COVID-19 pandemic on diagnostic delays in HPV-positive oropharyngeal cancer (OPC), and to describe their underlying reasons. METHODS: All HPV + OPC referred to a tertiary cancer centre and diagnosed between June-December 2019 (Pre-Pandemic cohort) vs June-December 2020 (Pandemic cohort) were reviewed. TNM classification, gross-tumor-volumes (GTV) and intervals between sign/symptom onset and treatment initiation were compared between the cohorts. Reasons for delay (>6 months from onset of signs/symptoms to a positive biopsy of the primary tumor, or a delay specifically mentioned in the patient chart) in establishing the diagnosis were recorded per clinician's documentation, and categorized as COVID-related or non-COVID-related. RESULTS: A total of 157 consecutive HPV + OPC patients were identified (Pre-Pandemic: 92; Pandemic: 65). Compared to the Pre-Pandemic cohort, Pandemic cohort patients had a higher proportion of N2-N3 (32 % vs 15 %, p = 0.019) and stage III (38 % vs 23 %, p = 0.034) disease at presentation. The differences in proportions with > 6 months delay from symptom onset to establishing the diagnosis (29 % vs 20 %, p = 0.16) or to first treatment (49 % vs 38 %, p = 0.22) were not statistically different. 47 % of diagnostic delays in the Pandemic cohort were potentially attributable to COVID-19. CONCLUSION: We observed a collateral impact of the COVID-19 pandemic on HPV + OPC care through more advanced stage at presentation and a non-significant but numerically longer interval to diagnosis. This could adversely impact patient outcomes and future resource allocation. Both COVID-19-related and unrelated factors contribute to diagnostic delays. Tailored interventions to reduce delays are warranted.

Extreme differences in SARS-CoV-2 Omicron viral loads among specimen types drives poor performance of nasal rapid antigen tests for detecting presumably pre-infectious and infectious individuals, predicting improved performance of combination specimen antigen tests (preprint)

Background. To limit viral transmission, COVID-19 testing strategies must evolve as new SARS-CoV-2 variants (and new respiratory viruses) emerge to ensure that the specimen types and test analytical sensitivities being used will reliably detect individuals during the pre-infectious and infectious periods. Our accompanying work demonstrated that there are extreme differences in viral loads among paired saliva (SA), anterior-nares swab (ANS) and oropharyngeal swab (OPS) specimens collected from the same person and timepoint. We hypothesized that these extreme differences may prevent low-analytical-sensitivity assays (such as antigen rapid diagnostic tests, Ag-RDTs) performed on a single specimen type from reliably detecting pre-infectious and infectious individuals. Methods. We conducted a longitudinal COVID-19 household-transmission study in which 228 participants collected SA, ANS, and OPS specimens for viral-load quantification by RT-qPCR, and performed an ANS Ag-RDT (Quidel QuickVue At-Home OTC COVID-19 Test) daily. We evaluated the performance of the Ag-RDT (n=2215 tests) to detect infected individuals (positive results in any specimen type by RT-qPCR) and individuals with presumed infectious viral loads (at or above thresholds of 10^4, 10^5, 10^6, or 10^7 copies/mL). Results. Overall, the daily Ag-RDT detected 44% (358/811) timepoints from infected individuals. From 17 participants who enrolled early in the course of infection, we found that daily Ag-RDT performance was higher at timepoints when symptoms were reported, but symptoms only weakly correlated with SARS-CoV-2 viral loads, so ANS Ag-RDT clinical sensitivity remained below 50%. The three specimen types exhibited asynchronous presumably-infectious periods (regardless of the infectious viral-load threshold chosen) and the rise in ANS viral loads was delayed relative to SA or OPS for nearly all individuals, which resulted in the daily ANS Ag-RDT detecting only 3% in the pre-infectious period and 63% in the infectious period. We evaluated a computationally-contrived combined AN-OP swab based on viral loads from ANS and OPS specimens collected at the same timepoint; when tested with similar analytical sensitivity as the Ag-RDT, this combined swab was predicted to have significantly better performance, detecting up to 82% of infectious individuals. Conclusion. Daily ANS rapid antigen testing missed virtually all pre-infectious individuals, and more than one third of presumed infectious individuals due to low-analytical-sensitivity of the assay, a delayed rise in ANS viral loads, and asynchronous infectious viral loads in SA or OPS. When high-analytical-sensitivity assays are not available and low-analytical-sensitivity tests such as Ag-RDTs must be used for SARS-CoV-2 detection, an AN-OP combination swab is predicted to be most effective for detection of pre-infectious and infectious individuals. More generally, low-analytical-sensitivity tests are likely to perform more robustly using oral-nasal combination specimen types to detect new SASR-CoV-2 variants and emergent upper respiratory viruses.

SARS-CoV-2 exhibits extreme differences in early viral loads among specimen types suggesting improved detection of pre-infectious and infectious individuals using combination specimen types (preprint)

Background. Screening testing, often via self-collected specimens, remains a key strategy to detect infections early and prevent SARS-CoV-2 transmission, and to enable earlier initiation of treatment. However, which specimen type best detects the earliest days of infection remains controversial. Further, the analytical sensitivity of diagnostic tests must also be considered, as viral loads below a test's limit of detection (LOD) are likely to yield false-negative results. Comparisons of quantitative, longitudinal SARS-CoV-2 viral-load timecourses in multiple specimen types can determine the best specimen type and test analytical sensitivity for earliest detection of infection. Methods. We conducted a COVID-19 household transmission study between November 2021 and February 2022 that enrolled 228 participants and analyzed 6,825 samples using RT-qPCR to quantify viral-load timecourses in three specimen types (saliva [SA], anterior-nares swab [ANS], and oropharyngeal swab [OPS]). From this study population, 14 participants enrolled before or at the incidence of infection with the Omicron variant. We compared the viral loads in specimens collected from each person at the same timepoint, and the longitudinal viral load timecourses from each participant. Using these viral loads, we inferred the clinical sensitivity of each specimen type to detect infected, pre-infectious and infectious individuals (based on presumably infectious viral load levels) using assays with a range of analytical sensitivities. We also inferred the clinical sensitivity of computationally contrived specimen types representing combinations of single specimen types. Results. We found extreme differences (up to 109 copies/mL) in viral loads between paired specimen types in the same person at the same timepoint, and that longitudinal viral load timecourses across specimen types did not correlate. Because of this lack of correlation, infectious viral loads were often observed in different specimen types asynchronously throughout the course of the infection. In the first 4 days of infection, no single specimen type was inferred to achieve >95% detection of infected or infectious individuals, even with the highest analytical sensitivity assays. In nearly all participants (11/14), a rise in ANS viral loads was delayed (as many as 7 days) relative to SA and OPS. We also observed that ANS and OPS had the most complementary viral load timecourses, resulting in optimal inferred performance with a computationally contrived combined anterior nares-oropharyngeal (AN-OP) swab specimen type. The combination AN-OP swab had superior inferred clinical sensitivity the first 8 days of infection with both high- and low-analytical-sensitivity assays. This AN-OP swab was also inferred to significantly improve detection of pre-infectious and infectious individuals over any single specimen type. Conclusion. Our work demonstrates that the viral load in one specimen type cannot reliably predict the viral load in another specimen type. Combination specimen types may offer a more robust approach for earliest detection of new variants and respiratory viruses when viral kinetics are still unknown.

A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis – ICE COVID (preprint)

Introduction: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in-vitro activity against SARS-CoV-2. This clinical trial was designed to investigate the efficacy of carrageenan nasal and throat sprays in reducing the rate and severity of COVID-19 infection. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Methods: and analysis: A single centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water) or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks.Primary outcome: Acquisition of COVID-19 infection as confirmed by positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. Hypothesis: That carrageenan spray will reduce SARS-CoV-2 attachment to the naso- and oropharyngeal mucosal epithelial cells thus reducing the effective viral infective dose preventing COVID19 infection and reducing disease severity where infection is not prevented. Ethics and dissemination : Ethics approval was obtained from Research Ethics Committee 6 South Wales (REC Reference 20/WA/0298; IRAS 283187) on the 18 th November 2020. The results will be submitted for publication in a peer-reviewed journal. Trial registration number: NCT04590365; registered on ClinicalTrials.gov (NCT04590365) on the 19 th October 2020.

Detection of SARS-CoV-2 in air and on surfaces in rooms of infected nursing home residents (preprint)

There is an ongoing debate on airborne transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as a risk factor for infection. In this study, the level of SARS-CoV-2 in air and on surfaces of SARS-CoV-2 infected nursing home residents was assessed to gain insight in potential transmission routes. During outbreaks, air samples were collected using three different active and one passive air sampling technique in rooms of infected patients. Oropharyngeal swabs (OPS) of the residents and dry surface swabs were collected. Additionally, longitudinal passive air samples were collected during a period of 4 months in common areas of the wards. Presence of SARS-CoV-2 RNA was determined using RT-qPCR, targeting the RdRp- and E-genes. OPS, samples of two active air samplers and surface swabs with Ct value [≤]35 were tested for the presence of infectious virus by cell culture. In total, 360 air and 319 surface samples from patient rooms and common areas were collected. In rooms of 10 residents with detected SARS-CoV-2 RNA in OPS, SARS-CoV-2 RNA was detected in 93 of 184 collected environmental samples (50.5%) (lowest Ct 29,5), substantially more than in the rooms of residents with negative OPS on the day of environmental sampling (n=2) (3.6%). SARS-CoV-2 RNA was most frequently present in the larger particle size fractions (>4 m 60% (6/10); 1-4 m 50% (5/10); <1 m 20% (2/10)) (Fischer exact test p=0.076). The highest proportion of RNA-positive air samples on room level was found with a filtration-based sampler 80% (8/10) and the cyclone-based sampler 70% (7/10), and impingement-based sampler 50% (5/10). SARS-CoV-2 RNA was detected in ten out of twelve (83%) passive air samples in patient rooms. Both high-touch and low-touch surfaces contained SARS-CoV-2 genome in rooms of residents with positive OPS (high 38% (21/55); low 50% (22/44)). In one active air sample, infectious virus in vitro was detected. In conclusion, SARS-CoV-2 is frequently detected in air and on surfaces in the immediate surroundings of room-isolated COVID-19 patients, providing evidence of environmental contamination. The environmental contamination of SARS-CoV-2 and infectious aerosols confirm the potential for transmission via air up to several meters.

Discovery of new salivary gland - A substantial histological analysis.

Regardless of the COVID-19 pandemic in 2020, discovering a new salivary gland turned into all the rage among the medical fraternity. The significance of the disclosure has been correlated with its clinical relevance in radiotherapy of oropharyngeal carcinoma. However, there are views against this new revelation, owing to the lack of substantial evidence. We have endeavoured to illuminate Tubarial glands with potential shreds of evidence.

The impact of the COVID-19 pandemic on hospitalizations for oral and oropharyngeal cancer in Brazil.

Timely diagnosis and treatment of oral and oropharyngeal cancers are central for the patient's survival. Our objective was to document the impact of the COVID-19 pandemic on the rate of hospitalizations due to these cancers in Brazil's National Health System (SUS). The number of hospitalizations by these cancers during the first periods of the pandemic-and between the same period of 2016 to 2019-was retrieved from the SUS Hospital Information System. We compared hospitalization rates between pre- and pandemic periods, by State. The hospitalization rate for oral and oropharyngeal cancer during the pandemic was lower than that of the same period of previous years. The decline between 2019 and 2020 was of 49.3%, reaching 60% in the North. The reduction in hospitalization during an extended period suggests that oral and oropharyngeal cancer care will be postponed, with potentially detrimental impact on survival.

Diagnostic accuracy of PanbioTM rapid antigen tests on oropharyngeal swabs for detection of SARS-CoV-2 (preprint)

Background Antigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients. Methods We conducted a prospective study in a single screening center to assess the diagnostic performance of the PanbioTM COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS. Results 402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a specificity of 99.1% (95%CI: 96.9-99.9) for the RDT. For cycle threshold values [≤] 26.7 ([≥] 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS. Interpretation Based on our findings, the diagnostic performance of the PanbioTM Covid-19 RDT with OPS samples meet the criteria required by the WHO for Ag-RDTs (sensitivity [≥] 80% and specificity [≥] 97%).

Diagnosis of SARS-Cov-2 infection using specimens other than naso- and oropharyngeal swabs: a systematic review and meta-analysis (preprint)

SUMMARY Background The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling, yet, with some limitations. Several specimens that are easier to collect are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/ posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab [CS]) against standard specimens (NPS, OPS, or a combination of both). Methods In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30 th of December 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. Methodological quality was assessed through the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2). Findings We identified 3022 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0-98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4-88.8) and specificity of 96.4% (95% CI: 89.5-98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3-95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3-96.9) and specificity of 63.1% (95% CI: 36.8-89.3). Remaining index specimens presented uncertainty given the lack of studies available. Interpretation Our meta-analysis shows that saliva samples from oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or outbreak control spots (e.g. schools, airports, and nursing homes). Funding Nothing to declare. Research in context Evidence before this study The lack of systematized data on the accuracy performance of alternative specimens for the detection of SARS-CoV-2 (against the standard NPS/OPS). The ever-growing number of studies available, made this updated systematic review timely and of the utmost importance Added value of this study Our meta-analysis shows that saliva samples from the oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial since DTS/POS samples may induce a higher rate of false positives. Implications of all the available evidence Saliva samples simply taken from the oral cavity are promising alternatives to the currently used nasal/throat swabs. Saliva specimens can be self-collected, mitigate the discomfort caused by sampling, reduce the transmission risk and increase testing capacity. Therefore, the validation of this alternative specimen will promote the implementation of truly deployable rapid tests for SARS-CoV-2 detection at the point-of-care or outbreak spots.

Diagnosis of SARS-CoV-2 Infection Using Specimens Other than Naso- and Oropharyngeal Swabs: A Systematic Review and Meta-Analysis (preprint)

Background: The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling, yet, with some limitations. Several specimens that are easier to collect are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/ posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab [CS]) against standard specimens (NPS, OPS, or a combination of both).Methods: In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30th of December 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. Methodological quality was assessed through the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2).Findings: We identified 3022 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0-98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4-88.8) and specificity of 96.4% (95% CI: 89.5-98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3-95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3-96.9) and specificity of 63.1% (95% CI: 36.8-89.3). Remaining index specimens presented uncertainty given the lack of studies available.Interpretation: Our meta-analysis shows that saliva samples from oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or outbreak control spots (e.g. schools, airports, and nursing homes).Funding Statement: This work was supported by national funds from FCT - Foundation for Science and Technology, I.P. through the CiiEM (project IDB/04585/2020), the Applied Molecular Biosciences Unit-UCIBIO (project UID/Multi/04378/2013), co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728) and the program Research4COVID 19 (Project nr. 662).Declaration of Interests: We declare no competing interests.

Time to Surgery and Survival in Head and Neck Cancer.

BACKGROUND: The COVID-19 pandemic has required triage and delays in surgical care throughout the world. The impact of these surgical delays on survival for patients with head and neck squamous cell carcinoma (HNSCC) remains unknown. METHODS: A retrospective cohort study of 37 730 patients in the National Cancer Database with HNSCC who underwent primary surgical management from 2004 to 2016 was performed. Uni- and multivariate analyses were used to identify predictors of overall survival. Bootstrapping methods were used to identify optimal time-to-surgery (TTS) thresholds at which overall survival differences were greatest. Cox proportional hazard models with or without restricted cubic splines were used to determine the association between TTS and survival. RESULTS: The study identified TTS as an independent predictor of overall survival (OS). Bootstrapping the data to dichotomize the cohort identified the largest rise in hazard ratio (HR) at day 67, which was used as the optimal TTS cut-point in survival analysis. The patients who underwent surgical treatment longer than 67 days after diagnosis had a significantly increased risk of death (HR, 1.189; 95% confidence interval [CI], 1.122-1.261; P < 0.0001). For every 30-day delay in TTS, the hazard of death increased by 4.6%. Subsite analysis showed that the oropharynx subsite was most affected by surgical delays, followed by the oral cavity. CONCLUSIONS: Increasing TTS is an independent predictor of survival for patients with HNSCC and should be performed within 67 days after diagnosis to achieve optimal survival outcomes.

COVID-19 and Total Laryngectomy-A Report of Two Cases.

OBJECTIVE: To date, no cases have been reported on the effects of COVID-19 in laryngectomees. CASE PRESENTATION: We herein presented two clinical cases of laryngectomized patients affected by COVID-19, detailing their clinical course and complications. DISCUSSION: In our experience, permanent tracheostomy did not significantly affect the choice of treatment. However, dedicated devices and repeated tracheal toilettes may be needed to deal with oxygen-therapy-related tracheal crusting. CONCLUSION: In conclusion, laryngectomees should be considered a vulnerable population that may be at risk for worse outcomes of COVID-19 due to anatomical changes in their airways. The role of the ENT specialist is to guide airway management and inform the support-staff regarding specific needs of these patients.

At-home self-collection of saliva, oropharyngeal swabs and dried blood spots for SARS-CoV-2 diagnosis and serology: post-collection acceptability of specimen collection process and patient confidence in specimens (preprint)

Background: Options to increase the ease of testing for SARS-CoV-2 infection and immune response are needed. Self-collection of diagnostic specimens at home offers an avenue to allow people to test for SARS-CoV-2 infection or immune response without traveling to a clinic or laboratory. Before this study, survey respondents indicated willingness to self-collect specimens for COVID-related tests, but hypothetical willingness can differ from post-collection acceptability after participants collect specimens. Methods: 153 US adults were enrolled in a study of the willingness and feasibility of patients to self-collect three diagnostic specimens (saliva, oropharyngeal swab (OPS) and dried blood spot (DBS) card) while observed by a clinician through a telehealth session. After the specimens were collected, 148 participants participated in a survey about the acceptability of the collection, packing and shipping process, and their confidence in the samples collected for COVID-related laboratory testing. Results: A large majority of participants (>84%) reported that collecting, packing and shipping of saliva, OPS, and DBS specimens were acceptable. Nearly nine in 10 (87%) reported being confident or very confident that the specimens they collected were sufficient for laboratory analysis. There were no differences in acceptability for any specimen type, packing and shipping, or confidence in samples by gender, age, race/ethnicity, or educational level. Conclusions: Self-collection of specimens for SARS-CoV-2 testing and preparing and shipping specimens for analysis were acceptable in a diverse group of US adults. Further refinement of materials and instructions to support self-collection of saliva, OPS and DBS specimens for COVID-related testing is needed.

Hypofractionated radiotherapy alone with 2.4 Gy per fraction for head and neck cancer during the COVID-19 pandemic: The Princess Margaret experience and proposal.

BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.