Persistent high-risk human papillomavirus (HPV) infection is one of the major etiologies of oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to determine the proportion, temporal trend, and prognostic significance of HPV-related OPSCC in Thai patients.

The study included patients with OPSCC who were treated at Songklanagarind Hospital (Songkhla, Southern Thailand) from 2009 to 2020. HPV status was screened by p16 expression using immunohistochemistry and confirmed by real-time polymerase chain reaction. Cox regression was used to determine prognostic significance.

The overall proportion of HPV+ OPSCC was 15.3% (95% confidence interval [CI]: 12.1-18.5) with a slightly increased proportion from 10.6% in 2009-2010 to 16.5% (2019-2020) (P for trend = 0.166). Among the HPV+ cases, HPV16 was detected in 65.3%, HPV18 in 34.7%, and other high-risk HPV types in 24%. Patients with P16+ or HPV+ OPSCC had significantly better overall survival (hazard ratio [HR]: 0.63, 95% CI: 0.45-0.90 and HR: 0.63, 95% CI: 0.45-0.88, respectively).

Thai patients in the southern region have a low proportion of HPV-related OPSCC with an increasing trend. Both P16 expression and HPV DNA status are strong independent prognostic factors of OPSCC.

Oropharyngeal squamous cell carcinoma is a prevalent neoplastic condition. The incidence rate in Malaysia is rising, with human papillomavirus (HPV) infection being recognized as a significant contributing factor. Hence, it is paramount for physicians to effectively diagnose and identify significant indicators that may indicate a malignant etiology. In this study, we present a case of a middle-aged Malay male who presented with the primary symptom of persistent right throat discomfort for one month. The preliminary presentation, blood parameters, and initial histopathological examination (HPE) findings indicate the presence of an infection. However, despite undergoing several medical treatments, the patient's symptoms remain, albeit with only minor clinical improvement. Subsequently, the patient underwent a biopsy under general anesthesia, which subsequently yielded a report indicating the presence of oropharyngeal squamous cell carcinoma with a negative p16 status. Therefore, it is imperative for clinicians to possess knowledge of warning flags and exercise vigilance when encountering a patient who fails to respond despite thorough and precise evaluation. If there is a strong suspicion of malignancy, it is imperative to do a comprehensive clinical investigation and regular monitoring.

In addition to the conventional aetiologic agents of oropharyngeal squamous cell carcinoma (OPSCC) such as tobacco usage, alcohol consumption and betel quid usage, it has been established that a proportion of OPSCC are driven by persistent oncogenic human papillomavirus (HPV) infections. Currently, there is a lack of data on the burden of HPV- associated OPSCC in Asian countries including Malaysia.

A cross-sectional multicentre study with tissue analysis of Malaysian patients diagnosed with primary OPSCC within a five-year period, from 2015 to 2019 between 01/01/2015 to 31/12/2019 was undertaken. Determination of HPV status was carried out using p16INK4a immunohistochemistry on tissue microarrays constructed from archived formalin-fixed paraffin-embedded tissue.

From the cases identified, 184 cases had sufficient tissue material for analysis. Overall, median age at diagnosis was 63.0 years (IQR = 15) and 76.1% of patients were males. In our cohort, 35.3% of patients were Indian, 34.2% were Chinese, 21.2% were Malay and 9.2% were from other ethnicities. The estimated prevalence of HPV-associated OPSCC in our cohort was 31.0% (CI 24.4-38.2%). The median age for the HPV-associated OPSCC sub-group of patients was not significantly lower than the median age of patients with HPV-independent OPSCC. More than half of HPV-associated OPSCC was seen in patients of Chinese ethnicity (54.4%). Patients with HPV-associated OPSCC had a much better overall survival than patients with HPV-independent OPSCC (Log rank test; p < 0.001). Patients with HPV-associated OPSCC with no habit-related risk factors such as smoking, were found to have much better overall survival when compared to all other sub-groups.

The findings from our study suggests that prevalence of HPV-associated OPSCC in Malaysia, though not as high as some developed countries, is however on an upward trend. HPV-associated OPSCC appears to be more frequently encountered in patients of Chinese ethnicity. Conventional risk-factors associated with OPSCC such as smoking, alcohol consumption and betel quid chewing should still be considered when estimating prognosis of patients with HPV-associated OPSCC.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia.

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.

Given the paucity of data and widely variable rates that have been reported, the main objective of this study was to examine the prevalence of HPV-positivity in oropharyngeal squamous cell carcinoma (OPSCC) in Middle Eastern patients presenting to one of the region's largest tertiary care centers using polymerase chain reaction (PCR) amplification of the HPV E6/E7 oncogenes, a highly sensitive and specific method of detection.

Medical charts and archived pathological specimens were obtained for patients diagnosed with biopsy proven oropharyngeal cancer who presented to the American University of Beirut Medical Center between 1972 and 2017. DNA was extracted from paraffin-embedded specimens and tested for 30 high-risk and low-risk papilloma viruses using the PCR-based EUROarray HPV kit (EuroImmun).

A total of 57 patients with oropharyngeal cancer were initially identified; only 34 met inclusion/exclusion criteria and were included in the present study. Most patients were males (73.5%) from Lebanon (79.4%). The most common primary tumor site was in the base of tongue (50%), followed by the tonsil (41.2%). The majority of patients (85.3%) tested positive for HPV DNA.

The prevalence of HPV-positivity amongst Middle Eastern OPSCC patients, specifically those from Lebanon, may be far greater than previously thought. The Lebanese population and other neighboring Middle Eastern countries may require a more vigilant approach towards HPV detection and awareness. On an international level, further research is required to better elucidate non-classical mechanisms of HPV exposure and transmission.

Human papillomavirus (HPV) is the most common sexually transmitted agent in the world. It can cause condyloma acuminatum, anogenital malignancies, and head and neck cancers. The host immune responses to HPV involve multiple cell types that have regulatory functions, and HPV-mediated changes to regulatory T cells (Tregs) in both the local lesion tissues and the circulatory system of patients have received considerable attention. The role of Tregs in HPV infections ranges from suppression of effector T cell (Teff) responses to protection of tissues from immune-mediated injury in different anatomic subsites. In this review, we explore the influence of Tregs in the immunopathology of HPV-related diseases and therapies targeting Tregs as novel approaches against HPV.