New Advances in Nasopharyngeal and Oropharyngeal Cancer Treatment

Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV⁺) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV⁺ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV⁻) OPC, certain HPV⁺ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV⁺ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV⁺ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1–T2 classification (89.3% vs. 72.0%; p = 1.1 × 10⁻²), stages I–II (92.1% vs. 82.2%; p = 4.6 × 10⁻²), and stages III–IV (82.8% vs. 62.2%; p = 5.7 × 10⁻²) and for HPV⁻ patients (85.5% vs. 33.3%; p < 1.0 × 10⁻⁶). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV⁺ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC. Full article

Background: The incidence of patients showing neck metastasis and no obvious primary tumor at the initial diagnostic evaluation or neck cancer of unknown primary (NCUP) is rising. It is estimated that a relevant part of these tumors arises in the tonsillar crypts or base of the tongue and are p16+-related. However, today, the detection rate of the primary tumor is suboptimal. Identifying the primary tumor and its biomolecular characterization is essential since it influences the treatment administered, possibly reducing radiation fields and providing de-escalation to primary surgical management. However, p16 IHC (immunohistochemistry) might not be sufficient to diagnose HPV-related OPSCC. The other subset of patients discussed are the HPV-positive patients who have a history of tobacco exposure and/or p53 mutations. Possible factors that could negatively influence the outcomes of these patients are investigated and discussed below. So, this paper aims to analyze the diagnostic, bio-molecular, clinico-radiological, morphological, prognostic and therapeutical aspects of p16-positive OPSCC, highlighting the possible bias that can occur during the diagnostic and prognostic process. Methods: A narrative review was conducted to investigate the biases in the diagnostic and therapeutic process of two groups of patients: those who are p16-positive but HPV-negative patients, and those who are p16-positive and HPV-positive with exposure to traditional risk factors and/or p53 mutations. The keywords used for the literature research included the following: NCUP, OPSCC, p16IHC, HPV testing, p16 positive HPV negative OPSCC, p16 positive HPV positive OPSCC, tonsillectomy, tobacco exposure, p53 mutations, cystic neck metastasis, extranodal extension (ENE), radiotherapy, de-escalation and neck neck dissection. Results: HPV-positive OPSCC has specific clinico-radiological features. Bilateral tonsillectomy should be considered for the identification of the primary tumor. P16 IHC alone is not sufficient for diagnosing HPV-related OPSCC; additional detection methods are required. The role of tobacco exposure and p53 mutations should be investigated especially in cases of HPV-positive tumors. Extranodal extension (ENE) must be taken into consideration in the prognostic staging of HPV-positive tumors. Surgical primary treatment involving neck dissection (ND) and bilateral tonsillectomy followed by adjuvant radiation may represent the most appropriate approach for N3 cases. Diagnosis, prognosis and therapeutical implications must be addressed considering clinical, biomolecular and morphological aspects. At least today, the numerous biases that are still present influencing the diagnostic and prognostic process do not permit considering de-escalation protocols. Conclusions: A precise and accurate diagnosis is required in order to adequately stage and manage p16+ OPSCC, particularly with neck metastasis. The role of tobacco exposure and/or p53 mutations must be considered not only in p16+ OPSCC but especially in HPV-positive OPSCC. Until a more accurate diagnosis is possible, ENE should be considered even in p16+HPV+ OPSCC. Primary surgery with unilateral ND and bilateral tonsillectomy might be the treatment of choice given the numerous diagnostic and prognostic pitfalls. Therefore, it is inappropriate and risky to propose de-escalation protocols in routine clinical practice due to the risk of undertreatment. Full article

Background: Transoral robotic surgery (TORS) is nowadays considered a valuable minimally invasive approach to treat oropharyngeal squamous cell carcinoma (OPSCC). The aim of this technique is to improve functional preservation and reduce morbidity with excellent oncologic outcomes compared to the traditional transoral approach and chemoradiotherapy (CRT). The purpose of this systematic review is to assess an exhaustive overview of functional outcomes of TORS for OPSCC by evaluating several parameters reported in the available literature, such as the prevalence and dependence of tracheotomy, feeding tubes (FTs) and percutaneous endoscopic gastrostomy (PEG), the length of hospitalization, swallowing scores, speech tests and quality of life (QoL) questionnaires. Methods: A systematic literature review has been performed following the PRISMA 2020 checklist statement. A computer-aided search was carried out using an extensive set of queries on the Embase/PubMed, Scopus and Web of Sciences databases relating to papers published from 2007 to 2024. Results: A total of 28 papers were systematically reviewed, reporting 1541 patients’ data. The mean time of hospitalization was 6 days. A planned tracheotomy was performed in 8% of patients with a mean time of removal of 8 days. The prevalence and dependence of FT was 60% and 10%, respectively. Moreover, the presence of a high-stage T tumor with the contextual requirement of adjuvant therapies, the involvement of base tongues and the patient’s age being >55 years increased the risk of requiring an FT and PEG. Swallowing and long-term QoL outcomes highlight the superiority of the TORS approach alone compared to TORS with adjuvant therapies. Conclusions: TORS presented various favorable functional outcomes compared to other surgical approaches and primary CRT. However, adjuvant therapies after TORS strongly reduced the advantage of the robotic procedure, thus suggesting that T1 and T2 tumors may benefit mainly from TORS alone. Full article