Accuracy of p16 IHC in Classifying HPV-Driven OPSCC in Different Populations

Gallus, Roberto; Nauta, Irene; Marklund, Linda; Rizzo, Davide; Crescio, Claudia; Mureddu, Luca; Tropiano, Paolo; Delogu, Giovanni; Bussu, Francesco

doi:10.3390/cancers15030656

Cited by 6 publications

(4 citation statements)

References 53 publications

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“…In addition to the p16 + /HPV + cases we could identify in total 62 patients with p16 overexpression but HPV-DNA negative OPSCC (which is a rate of 4.9% of false positive p16 cases).This rate is comparable with the predicted rate of false positive p16 cases (3.8%) calculated by a recently published formula of Gallus et al [ 42 ]. Recent studies [ 9 , 37 , 40 – 42 ] found that patients with p16 + /HPV- OPSCC seem to have the same prognosis or only slightly better than p16-/HPV- cases. Consistent with these findings patients in our cohort with p16 + /HPV- OPSCC (and p16-/HPV + OPSCC) had a significant worse OS than patients with p16 + /HPV + OPSCC (additional Fig.…”

Section: Discussionsupporting

confidence: 74%

“…This is important to emphasize, as the definition of HPV positive OPSCC (whether it is defined only by overexpression of p16, independent of HPV-DNA or a combination of HPV-DNA and p16 positivity) is still discussed controversially in literature and not uniform [ 9 , 37 , 40 – 42 ]. In addition to the p16 + /HPV + cases we could identify in total 62 patients with p16 overexpression but HPV-DNA negative OPSCC (which is a rate of 4.9% of false positive p16 cases).This rate is comparable with the predicted rate of false positive p16 cases (3.8%) calculated by a recently published formula of Gallus et al [ 42 ]. Recent studies [ 9 , 37 , 40 – 42 ] found that patients with p16 + /HPV- OPSCC seem to have the same prognosis or only slightly better than p16-/HPV- cases.…”

Section: Discussionmentioning

confidence: 99%

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Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study

Klasen,

Wuerdemann,

Rothbart

et al. 2023

BMC Cancer

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Background Oropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors. Methods This retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8th edition (AJCC8), HPV status, treatment modality (surgery (± radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis. Results With the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (± R(C)T) – vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003). Conclusion Sex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study

Klasen,

Wuerdemann,

Rothbart

et al. 2023

BMC Cancer

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“…This has a potential detrimental effect on patient stratification and selection for deintensification protocols in these populations, and it could, theoretically, also affect HPV detection in subsites other than the oropharynx, where the HPV reported prevalence is often low. In fact, an ever-growing amount of evidence discourages its use as a surrogate marker of HPV infection outside of the oropharyngeal site and, in particular, in LSCCs, as well as under specific conditions (a low prevalence of HPV-related oropharyngeal squamous cell carcinoma), even for the oropharyngeal site [ 5 , 14 , 59 , 60 , 61 , 62 ]. The last decade of research on the topic seems to also minimize its potential biologic role in the cancerogenic process of LSCCs, probably impacting only a small subgroup of patients.…”

Section: P16 Ink4amentioning

confidence: 99%

p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?

Gallus,

Rizzo,

Rossi

et al. 2024

Pathogens

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Laryngeal squamous cell carcinoma (LSCC) is a common malignancy that, despite scientific advancements, has not seen an improvement in its prognosis in the last decades. Few promising predictive markers have been found and none are relevant in clinical practice. p16ink4a, an oncosuppressor protein involved in cell cycle arrest, with a prognostic impact on other cancers, has been widely used in the head and neck region as a surrogate marker of HPV infection. Published papers and recent meta-analyses seem to minimize the biological role of HPV in the context of LSCC’s cancerogenesis, and to disprove the reliability of p16ink4a as a surrogate prognostic marker in this context, while still highlighting its potential role as an independent predictor of survival. Unfortunately, the available literature, in particular during the last two decades, is often not focused on its potential role as an independent biomarker and few relevant data are found in papers mainly focused on HPV. The available data suggest that future research should focus specifically on p16ink4a, taking into account both its potential inactivation and overexpression, different patterns of staining, and immunohistochemistry cutoffs, and should focus not on its potential role as a surrogate marker but on its independent role as a predictor of survival.

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“…Therefore, the correct definition of HPV-driven carcinogenesis as part of the work-up is of paramount importance, and the possibility of false-positive findings at sole p16immunohistochemistry should not be underestimated [80,81]. In populations with a rate of HPV-driven SCC in the oropharynx below 40%, p16 overexpression should be integrated with nucleic acid detection to confirm HPV-driven carcinogenesis and draw proper clinical considerations [82,83].…”

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confidence: 99%

Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications

Caldarella,

De Risi,

Massaccesi

et al. 2024

Cancers

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This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head–neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs.

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Accuracy of p16 IHC in Classifying HPV-Driven OPSCC in Different Populations

Cited by 6 publications

References 53 publications

Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study

Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study

p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?

Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications

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