Salivary HPV Persistence Following Treatment of Oropharyngeal Squamous Cell Carcinoma

2021 ◽  
pp. 000348942110556
Author(s):  
Alexandra E. Quimby ◽  
Pagona Lagiou ◽  
Bibiana Purgina ◽  
Martin Corsten ◽  
Stephanie Johnson-Obaseki
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Cancer Center ◽  
Study Cohort ◽  
Curative Intent ◽  
Cross Sectional ◽  
Hpv Dna

Objective: To determine the persistence of human papillomavirus (HPV) infection following treatment of HPV-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC). Methods: A cross-sectional study was undertaken at The Ottawa Hospital (Ottawa, ON, Canada), a tertiary academic hospital and regional cancer center. Adult patients who were diagnosed with HPV + OPSCC between the years of 2014 and 2016 and treated with curative intent, and who were alive and willing to consent were eligible for inclusion. A saliva assay was used to test for the presence of HPV DNA in a random sample of patients. qPCR was used to amplify DNA from saliva samples. Results: Saliva samples were obtained from 69 patients previously treated with HPV + OPSCC. All patients had a minimum of 2 years of follow-up. 5 patients tested positive for HPV: 2 were positive for HPV-16, 2 for HPV-18, and 1 “other” HPV type. No patient in our study cohort had suffered recurrence post-treatment. Conclusions: This study is the first to demonstrate the prevalence of persistent oncogenic HPV DNA in saliva following treatment for HPV + OPSCC. This prevalence appears to be low, despite the fact that persistent HPV infection is a precursor for the development of HPV + OPSCC. This finding raises questions about what factors influence the clearance or persistence of HPV DNA in saliva after treatment for HPV + OPSCC, and may add to our understanding about the longitudinal effects of HPV infection in these cancers.

Outcomes of relapsed human papillomavirus‐related oropharyngeal squamous cell carcinoma treated with curative intent

Head & Neck ◽  
2018 ◽  
Vol 41 (5) ◽  
pp. 1312-1319 ◽  
Author(s):  
Patrik Pipkorn ◽  
Parul Sinha ◽  
Dorina Kallogjeri ◽  
Douglas Adkins ◽  
Wade T. Thorstad ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Curative Intent

scholarly journals Human Papillomavirus and Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study regarding Tobacco and Alcohol Consumption

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
F. Farshadpour ◽  
S. Konings ◽  
E. J. M Speel ◽  
G. J. Hordijk ◽  
R. Koole ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Stage ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Fish Analysis ◽  
Hpv Dna ◽  
Negative Tumor ◽  
Matching Criteria

We aimed to determine the role of HPV in the pathogenesis and outcome of oropharyngeal squamous cell carcinoma (OSCC) in lifelong nonsmoking and nondrinking patients. A case-case analysis was performed to compare the presence of HPV-DNA in tumor cells of 16 nonsmoking and nondrinking with 16 matched smoking and drinking patients (matching criteria: age at incidence, gender, tumor sublocation, tumor stage). HPV was detected using 2 PCR tests, FISH analysis, and p16INK4A immunostaining. Nonsmoking and nondrinking patients had more HPV-positive tumors than smoking and drinking patients (n=12; 75% versus n=2; 13%; P<0.001). All HPV-positive tumors showed p16INK4A overexpression, and 1 HPV-negative tumor had p16INK4A overexpression, (P<0.001). Overall survival and disease-specific survival were higher for HPV-positive compared to HPV-negative cases (P=0.027, P=0.039, resp.). In conclusion, HPV is strongly associated with OSCC of nonsmoking and nondrinking patients. Specific diagnostic and therapeutic actions should be considered for these patients to achieve a better prognosis.

scholarly journals Prevalence of Human Papillomavirus Associated with Head and Neck Squamous Cell Carcinoma in Jordanian Patients

2020 ◽  
Vol 14 (1) ◽  
pp. 57-64
Author(s):  
Ashraf I. Khasawneh ◽  
Nisreen Himsawi ◽  
Jumana Abu-Raideh ◽  
Muna Salameh ◽  
Niveen Abdullah ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Prophylactic Measures

Background: In addition to smoking and alcohol consumption, human papillomavirus (HPV) is a leading etiology for Head and Neck Squamous Cell Carcinoma (HNSCC). However, this causal association is still understudied in Middle Eastern populations. Objective: The aim of this study was to determine the prevalence of HPV-associated infection in the Jordanian HNSCC patients and the associated HPV genotypes. Methods: Formalin-Fixed Paraffin-Embedded (FFPE) squamous cell carcinoma samples of the head and neck were collected from two referral centers in Amman, Jordan to determine the existence of HPV DNA. After DNA extraction HPV infection and genotyping were identified using real-time PCR. Results: HPV DNA was detected in 19 out of 61 (31.1%) HNSCC samples. Despite screening for 28 different genotypes, HPV 16 was the only genotype identified in all examined samples. Most HPV-positive samples were obtained from the oropharynx (41.7%), oral cavity (37%), and larynx (18.2%). No significant association between HPV 16 genotype and age, sex, tobacco use, anatomical location, or tumor grade was noticed. Conclusion: This study reported a high association between HPV 16 genotype and HNSCC in Jordanian patients. These data should facilitate the implementation of appropriate HPV awareness campaigns, and activate selective prophylactic measures against HPV infection.

scholarly journals Expression of p16 and Galectin3 in Squamous Cell Carcinoma of Uterine Cervix, in Relation to the Histomorphological Variants: A Cross-sectional Analysis

2021 ◽  
Author(s):  
Sarbashis Hota ◽  
Tushar Kanti Das
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Uterine Cervix ◽  
Tumour Microenvironment ◽  
Hpv Infection ◽  
Tumour Grade ◽  
Cross Sectional ◽  
P16 Expression

Introduction: Cancer of uterine cervix comprises a big chunk of cancer registration worldwide. Now-a-days the immunohistochemical marker p16 has emerged as the surrogate marker of high risk Human Papilloma Virus (HPV) infection in cervical tissue. Galectin3, a ubiquitous agent likely to modulate different pro-survival properties necessary for neoplastic cells, is recently emerging as the guardian of tumour microenvironment. Aim: To study the expression of p16 and galectin3 in different histomorphological variants of cervical Squamous Cell Carcinoma (SCC) and their association with grade and stage. Materials and Methods: An observational cross-sectional study was undertaken in the Department of Pathology in a tertiary care hospital in East India, from January, 2019 to June, 2020. Fifty three samples diagnosed as invasive Squamous Cell Carcinoma (SCC) of uterine cervix were taken by systematic random sampling. Immunohistochemical examination was done using monoclonal antibodies against p16 and galectin3 after obtaining thin sections from formalin fixed paraffin embedded blocks and retrieval of antigen. The data was interpreted by light microscopy using a semiquantitative method with respect to prefixed parameters and statistical analysis was done by chi-square test and Fisher’s exact test using SPSS version 25.0. Results: Fifty two out of fifty three cases (98.1%) of squamous cell carcinoma in this study showed almost 100% block posivity of p16 in the tumour cells -strongly corroborative with high risk HPV infection. The non-keratinizing and the basaloid variant showed the strongest intensity of staining (3+). Only one case showed complete negativity of p16 expression. In galectin3 positive cases, strong expression of this marker is found in the invasive tongues of the tumour cells at the junction of tumour stromal interface, consistent with our knowledge regarding the importance of galectin3 in regulating the tumour microenvironment. The strongest galectin3 positivity(3+) was found in the single case of Lymphoepithelioma like squamous cell carcinoma and showed almost 100% positivity among the neoplastic cell population; whereas the non-keratinizing and Basaloid variant showed almost negative expression. Significant association (p=0.00021) found between tumour grade and p16 intensity. Conclusion: The non-keratinizing and basaloid variants of squamous cell carcinoma have shown statistically significant association with highest intensity of p16 staining along with diminished expression of galectin3. Increased tumour grade is also significantly associated with strong staining intensity of p16 and decreased galectin3 expression. However, no significant association is found between galectin3 expression or intensity of p16 expression and the stage of tumour.

scholarly journals Evolving Treatment Paradigms for Oropharyngeal Squamous Cell Carcinoma

2018 ◽  
pp. 1-9
Author(s):  
Ryan K. Cleary ◽  
Anthony J. Cmelak
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
The United States ◽  
Hpv Infection ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Distinct Disease ◽  
Risk Patients ◽  
Traditional Risk Factors ◽  
Distinct Disease Entity

Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence in the United States and in many countries worldwide primarily as a result of increasing rates of human papillomavirus (HPV) infection. HPV-positive OPSCC represents a distinct disease entity from head and neck squamous cell carcinoma caused by traditional risk factors such as tobacco and alcohol, with different epidemiology, patterns of failure, and expected outcomes. Because patients with HPV-positive OPSCC have a younger median age and superior prognosis compared with their HPV-negative counterparts, they live longer with the morbidity of treatment, which can be severe. Therefore, efforts are under way to de-escalate therapy in favorable-risk patients while maintaining treatment efficacy. Additional work is being undertaken to discover new therapies that may benefit both HPV-positive and HPV-negative patient subsets. Herein, we will review the available data for the evolving treatment paradigms in OPSCC as well as discuss ongoing clinical trials.

Evaluating a clinically validated circulating tumor HPV DNA assay in saliva as a proximal biomarker in HPV+ oropharyngeal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6063-6063
Author(s):  
Sophie P. Gerndt ◽  
Ricardo J. Ramirez ◽  
Benjamin M. Wahle ◽  
Charlotte Kuperwasser ◽  
Alicia Gunning ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Tissue ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Wilcoxon Test ◽  
Viral Dna ◽  
Hpv Dna ◽  
History Of ◽  
Pre Treatment

6063 Background: HPV genomic DNA in plasma and saliva has been widely studied, however more recently, circulating tumor human papillomavirus DNA (ctHPVDNA) has emerged as a reliable biomarker for surveillance in HPV+ oropharyngeal squamous cell carcinoma (OPSCC). A commercial assay for this biomarker distinguishes tumor-derived viral DNA (tumor-tissue modified viral DNA or TTMV) from other non-cancer associated sources of HPV DNA. The use of this technology has been previously described in plasma, but its utility in saliva is currently unknown. Methods: A prospectively collected and banked biospecimen repository was used to identify 46 patients with HPV+ OPSCC with paired pre treatment plasma and saliva samples. All samples were assessed for DNA integrity and TTMV using a clinically validated ddPCR-based assay (NavDx™; Naveris Inc, Natick, MA) to measure TTMV for HPV-16, -18, -31, -33 and -35 from frozen plasma and saliva samples. Retrospective chart review was performed to collect clinical and pathological data. Graphpad was used for statistical analysis. Spearman’s r was used to correlate TTMV copies in saliva and plasma. Wilcoxon test was used to compare between sample types. Mann-Whitney test was used for categorical variables. Results: TTMV DNA was detectable in 43 of 46 plasma samples and in 44 of 46 saliva samples. One plasma sample failed quality control measures, one of each sample type had undetectable TTMV, and one of each type was indeterminate. Of 41 evaluable patients with paired samples, there were 38 (93%) males, 36 (88%) were stage I-II, 5 (12%) were stage III-IV (AJCC 8th, clinical staging), and 25 (61%) had a history of smoking with a median of 37.5 pack years. TTMV was significantly enriched in saliva compared to plasma (p<0.0001), with median copy number 14,139 copies/ml (IQR=193,339.5) and 774.7 copies/ml (IQR=4,826.1), respectively. There was a significant positive correlation between plasma and saliva TTMV levels (r=0.344, p=0.028). There was no difference in overall stage for either specimen type. There was a trend in both sample types toward higher TTMV in patients with a history of smoking. Pack-year history was available for 38 (93%) patients in the final cohort. When grouping by pack-years, plasma TTMV approached significance (p=0.058) while high saliva TTMV was significantly associated with >10 pack-year history (p=0.011). Conclusions: This is the first study to demonstrate successful quantification of tumor-tissue modified HPV DNA in saliva. Compared to plasma, pre treatment saliva samples demonstrated significantly higher levels of TTMV. TTMV distinguishes ctHPVDNA from other sources of HPV. These data highlight the potential use of TTMV detection in saliva for early detection of HPV+ OPSCC as well as its potential role in local surveillance after treatment. More research is needed to elucidate the effects of smoking on TTMV levels.

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