Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic important adjustments have been introduced in the healthcare settings to avoid hospital outbreaks and ensure necessary resources for COVID-19 patients. These included partial or complete interruption of diagnostic workflows, elective treatments, and management of routine follow-ups (1). Although those policies were targeted mainly to more deferrable activities, the COVID-19-related containment strategies are likely to have also affected the most vulnerable groups of patients and those requiring time-critical access to healthcare service, such as patients with cancer.

COVID-19 has triggered a decline in referral, diagnosis and treatment for cancer patients all over the world (2–5), raising concerns about a substantial increase in the number of avoidable cancer deaths in the near future (6). Nationally and locally imposed restrictions, guidelines for management of patients during different pandemic waves, changes in health-seeking behavior and the perception that hospitals are high-risk areas in terms of COVID-19 transmission risk, are all likely to have contributed to the observed reductions in the number of newly diagnosed cancer cases during the pandemic (7).

Head and neck cancers (HNC) are characterized by relatively fast growth, and timely diagnosis with prompt treatment initiation are essential for optimal oncologic outcomes in these patients (8). The effects of delayed HNC diagnosis and treatment are both immediate and long-term, and are expected to result in more advanced stages at presentation, an increased risk of relapse, worse treatment response and decreased short- and long-term survival (9). Patients with HNC are often diagnosed at an advanced stage, with previously reported prevalence of stage III-IV disease of 55 and 60% within the European ARCAGE and the UK HN5000 study, respectively (10, 11). Delays in the diagnosis and treatment of HNC due to the COVID-19 pandemic have been reported in several countries (12–16), causing more admissions in advanced stage disease and an increase in more complex reconstructive procedures.

Assessing the impact of COVID-19 on timely HNC diagnosis and treatment is complex, and the analyses must consider underlying temporal trends in admissions. Moreover, it is necessary to wait long enough to evaluate whether the COVID-19 impact has been limited to the first pandemic wave only or has lasting effects. Addressing the delayed diagnoses and treatment backlogs caused by the pandemic may take significant time to return to the pre-pandemic levels, contributing further to the existing healthcare crisis and increasing the number of potentially avoidable deaths due to cancer.

This study aimed at evaluating the temporal trends in HNC detection in the Piedmont Region, Italy, before and during the COVID-19 pandemic to indirectly assess the impact of COVID-19 on timely HNC diagnosis and treatment. Taking advantage of an ongoing HEADSpAcE study (17) recruitment, which had started in one of the largest tertiary care hospitals in Piedmont before the COVID-19 pandemic, we analyzed the stage at diagnosis of incident HNC in the pre-COVID-19 period of recruitment and in the periods following the COVID-19 outbreak.

The COVID-19 pandemic has hampered healthcare systems in many countries with significant effects on the management of patients with cancer (21). Using an interrupted time-series analysis, we showed that the initial reduction of 28% in admissions for incident HNCs in the Italian region Piedmont, during the first wave of the COVID-19 pandemic, was almost completely addressed by the end of 2020. The overall trend with a sharp decline during the first pandemic wave and the subsequent increase with the cumulative numbers reaching those expected for 2020 were also observed in the analyses stratified by tumor subsites and in patients <75 years. Our findings also indicate that the pandemic has affected certain groups of patients differentially. In particular, COVID-19 caused a notable decline in diagnosis of older patients (≥75 years), patients with less comorbidities, and those treated surgically. This gap between observed and expected numbers was only partially addressed by the end of 2020, likely due to the emerging second pandemic wave in autumn 2020. During the first pandemic wave people were generally advised to stay at home and avoid presenting at their physicians and emergency departments for non-urgent conditions. It is possible that patients with generally good health status (less comorbidities) sustained ignoring initial warning cancer signs and that the created backlog in the detection of HNC in these patients will be addressed only subsequently. An observed decline in patients with primary surgical treatment can, at least partially, be explained by the reduced hospital activity and the guidelines that recommended avoidance of clinical examinations and procedures presumed to be high-risk by potentially aerosolizing the virus, such as endoscopic procedures and tracheostomy (22–24).

Delayed HNC diagnosis is generally driven by patient-related factors (low educational attainment, low socioeconomic position, fear), healthcare system factors, and disease-related factors (length of the asymptomatic period, tumor subsite, HPV status) (25–28). The crisis that COVID-19 imposed on healthcare systems and individual changes in healthcare utilization and health-seeking behaviors have likely enhanced most of the existing barriers to timely diagnosis. Moreover, the increased overall mortality due to COVID-19 that was experienced by the Piedmont population (29), especially by older and the most vulnerable individuals, such as patients with cancer, may have acted as a competing phenomenon, preventing either the diagnosis or the first hospital admission of some patients. This is further supported by our finding of a particularly strong decline in diagnosis of patients ≥75 years, which was not completely recovered by the end of 2020.

In the secondary analysis of patients eligible for recruitment in an ongoing study, there was no evidence of an increase in diagnoses at advanced stage in the periods following the first pandemic wave. This is in line with a recent finding of no increased total laryngectomy volume, reserved for advanced cases, during the COVID-19 pandemic (30). Although these findings indicate no evident stage migration, it should be considered that the 10-month period after the start of the pandemic may still be limited to observe any change in the distribution of stages at diagnosis.

Several previous studies that reported COVID-19-related reductions in HNC admissions and diagnoses (12–16, 31, 32) were hospital-based studies, conducted on a relatively limited population, focused on the first pandemic wave only, and did not account for temporal trends in HNC detection. The reported reductions in HNC referrals and diagnoses in the first pandemic months varied from 12% to up to 60% in different contexts and populations (13, 15, 16, 30, 31). In this study, accounting for temporal trends over a relatively long period and seasonal (likely holiday-related) fluctuations in HNC admissions, we found a decline of 28% in incident HNC admissions during the first pandemic wave, which was almost completely recovered in 2020. The analysis on the subgroup of patients with information on stage at diagnosis supports these findings, as we did not find evidence of a shift toward more advanced diseases at diagnosis in the months after the first pandemic wave. Our findings are based on HDRs from a population of more than 4 million inhabitants, which is one of the largest studies so far assessing the impact of COVID-19 on HNC admissions/diagnoses. These findings also demonstrate a resilience of the Piedmont healthcare system showing that the very difficult experiences of the first pandemic wave were not protracted and that there was a bounce back recovery in the management of patients with HNC.

Limitations of the current study include common flaws of studies using routinely collected administrative data, such as accuracy of data coding and limited clinical information. In particular, we had no data on the stage at diagnosis for the analysis on all incident HNC admissions in Piedmont. For this reason, we complemented the analysis with the results of a subgroup of patients undergoing an active recruitment for whom this information was available. Even if this group was relatively small, information on stage was of high quality as each patient was staged specifically for this study based on available pathological and clinical data. Another point to consider is the possible misclassification of the tumor subsites within the broader HNC category. Although we believe that our algorithm identified almost all HNC admissions, it is possible that a definite ICD-9 diagnosis was not established during the first HNC admission. Nevertheless, any such misclassification would only influence our null results of the analysis stratified by tumor subsite and would not affect the overall study findings. Finally, we believe that HNC diagnoses outside hospitals, potentially not captured by HDRs, are minor, as in case of a suspicion of HNC, general practitioners and dentists (both public and private) refer patients, almost exclusively, toward specialized hospitals, where both the biopsy and the pathologic report can be performed at one place.

Here, we report the temporal trends in the incident HNCs in the first 10 months of the COVID-19 pandemic, in one of the largest Italian regions. Although an initial drop in the HNC admissions has been mostly recovered in this period, we found substantial differences in some patient subgroups. The impact of the COVID-19 on HNC observed in this study is potentially only the tip of the iceberg—the long-term effects of the pandemic on oncological outcomes and healthcare systems remain to be determined.

The raw data supporting the conclusions of this article will be made available by the corresponding author, upon reasonable request.

The studies involving human participants were reviewed and approved by Ethics Committee of the University of Turin. The patients/participants of the HEADSpAcE study provided their written informed consent to participate in this study.

MP: had full access to all the data in the study, takes responsibility for the integrity of the data, the accuracy of the data analysis, and drafting of the manuscript. LR and MP: concept and design. MP, LR, VF, CM, GM, and MG: acquisition and analysis. MP, LR, and GM: statistical analysis. All authors: interpretation of data and critical revision of the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.

This study received funding from the European Union's Horizon 2020 Research and Innovation Program under Grant Agreement No. 825771 (HEADSpAcE project), and from the Italian Ministry for Education, University and Research (Ministero dell'Istruzione, dell'Università e della Ricerca—MIUR) under the programme Dipartimenti di Eccellenza 2018–2022.

Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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