Papillary Squamous Cell Carcinoma of the Cervix: Human Papillomavirus (HPV) Status and Clinicopathologic Features

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S24-S24
Author(s):  
S A Schechter ◽  
A Elshaikh ◽  
H Walline ◽  
S L Skala
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clinical Stage ◽  
Hpv Infection ◽  
Low Grade ◽  
Cervical Neoplasm ◽  
Hpv Status ◽  
Papillary Squamous Cell Carcinoma

Abstract Introduction/Objective Papillary squamous cell carcinoma (PSCC) is a rare cervical neoplasm composed of papillae lined by atypical squamous/transitional cells without koilocytosis. It is unclear whether PSCC is related to human papillomavirus (HPV) infection, though rare cases were reportedly associated with HPV type 16. PSCC is thought to be more common in postmenopausal women. Some authors have suggested that PSCC may be understaged due to the prominent exophytic nature of the superficial aspect and relatively deep location of underlying infiltrative nests. It has also been suggested that PSCC has a tendency to recur and/or metastasize late. Methods The surgical pathology database of a single large academic institution was searched for squamous cell carcinoma (or squamous cell carcinoma in situ) with papillary features from the cervix, sampled between 1996 and 2018. PCR for human papillomavirus (HPV) L1 protein was run, with sequencing of positive samples. Results 5 cases diagnosed as “papillary squamous cell carcinoma” were identified. Patient age ranged from 21–63 years (mean 46 years). All tumors showed papillary architecture, often with complex branching and/or fusion. The neoplastic cells had a squamous/transitional appearance with moderate to marked cytologic atypia and at most focal keratinization. Stage ranged from pT1b1 to pT3b (clinical stage IB1 to IVB). HPV L1 PCR was positive in only one case; sequencing confirmed HPV type 16. Upon closer review, the HPV-positive case was from the youngest patient and showed adjacent low-grade squamous intraepithelial lesion (LSIL) as well as focal koilocytic change within the papillary tumor. Conclusion Our findings suggest that even in patients with HPV infection, PSCC may be an HPV-independent malignancy. In multiple cases, it was difficult to obtain definitive histologic evidence of invasion prior to resection.

scholarly journals Ancillary Studies in Determining Human Papillomavirus Status of Squamous Cell Carcinoma of the Oropharynx: A Review

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Richard L. Cantley ◽  
Eleonora Gabrielli ◽  
Francesco Montebelli ◽  
David Cimbaluk ◽  
Paolo Gattuso ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Significant Proportion ◽  
Hpv Infection ◽  
P16 Immunohistochemistry ◽  
Hpv Status ◽  
High Risk Hpv ◽  
Ancillary Studies

Squamous cell carcinoma (SCC) of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV) infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated. Nevertheless, significant overlap in morphology is seen between these two forms of SCC. The purpose of this paper is to highlight the utility of ancillary studies in the establishment of HPV status of oropharyngeal SCC, including p16 immunohistochemistry, high-risk HPV in situ hybridization, polymerase chain reaction, and newer HPV detection modalities.

scholarly journals p16 Protein Expression and Human Papillomavirus Status As Prognostic Biomarkers of Nonoropharyngeal Head and Neck Squamous Cell Carcinoma

2014 ◽  
Vol 32 (35) ◽  
pp. 3930-3938 ◽  
Author(s):  
Christine H. Chung ◽  
Qiang Zhang ◽  
Christina S. Kong ◽  
Jonathan Harris ◽  
Elana J. Fertig ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hpv Infection ◽  
P16 Protein ◽  
Hazard Ratios ◽  
Hpv Status ◽  
P16 Expression

Purpose Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. Patients and Methods p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. Results p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes. Conclusion Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.

Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: Analysis of the National Cancer Database.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 735-735
Author(s):  
Jaymin Jhaveri ◽  
Lael Rayfield ◽  
Yuan Liu ◽  
Mudit Chowdhary ◽  
Richard John Cassidy ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hpv Infection ◽  
National Cancer Database ◽  
Anal Squamous Cell Carcinoma ◽  
Prognostic Relevance ◽  
Hpv Status ◽  
The Impact

735 Background: To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation in the National Cancer Database (NCDB). Methods: The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV-. Univariate analysis was performed using the χ2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HR) and 95% confidence intervals (CI) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. Results: A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n = 498, 46.8%) and HPV- (n = 565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR 0.60, CI 0.38-0.96; p = 0.034). However, for women, HPV infection did not significantly influence survival (HR 1.47, CI 0.96-2.25; p = 0.074). Conclusions: To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.

scholarly journals Tobacco exposure as a major modifier of oncologic outcomes in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hesham Elhalawani ◽  
Abdallah S. R. Mohamed ◽  
Baher Elgohari ◽  
Timothy A. Lin ◽  
Andrew G. Sikora ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Oncologic Outcomes ◽  
Tobacco Exposure ◽  
Hpv Status

Abstract Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-virally mediated OPSCC, this effect is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients. Methods We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002–2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p < 0.05). Results Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p = 0.002, p = 0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ > 30 PY patients didn’t differ significantly from HPV- patients (p = 0.72, p = 0.27, respectively). HPV+ > 30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p = 0.03, 76% vs 88.3%; p = 0.07, and 52.3% vs 74%; p = 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively. Conclusions Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV + OPSCC smokers should be avoided.

scholarly journals Expression and Role of E-Cadherin, β-Catenin, and Vimentin in Human Papillomavirus–Positive and Human Papillomavirus–Negative Oropharyngeal Squamous Cell Carcinoma

2020 ◽  
Vol 68 (9) ◽  
pp. 595-606
Author(s):  
Hesham Mohamed ◽  
Caj Haglund ◽  
Lauri Jouhi ◽  
Timo Atula ◽  
Jaana Hagström ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Vimentin Expression ◽  
Regional Metastasis ◽  
E Cadherin

Oropharyngeal squamous cell carcinoma (OPSCC) is subclassified by the World Health Organization into two different entities: human papillomavirus (HPV)-positive and HPV-negative tumors. HPV infection promotes the epithelial-to-mesenchymal transition (EMT) and transformation of keratinocyte stem cells into cancer stem cells. EMT is a crucial process in the carcinogenesis of epithelial-derived malignancies, and we aimed to study the role of its markers in OPSCC. This study consists of 202 consecutive OPSCC patients diagnosed and treated with curative intent. We examined E-cadherin, β-catenin, and vimentin expression using immunohistochemistry and compared these with tumor and patient characteristics and treatment outcome. We found that the cell-membranous expression of β-catenin was stronger in HPV-positive than in HPV-negative tumors, and it was stronger in the presence of regional metastasis. The stromal vimentin expression was stronger among HPV-positive tumors. A high E-cadherin expression was associated with tumor grade. No relationship between these markers and survival emerged. In conclusion, β-catenin and vimentin seem to play different roles in OPSCC: the former in the tumor tissue itself, and the latter in the tumor stroma. HPV infection may exploit the β-catenin and vimentin pathways in carcinogenic process. More, β-catenin may serve as a marker for the occurrence of regional metastasis:

Socioeconomic and Racial Disparities and Survival of Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

2020 ◽  
pp. 019459982093585
Author(s):  
Janine M. Rotsides ◽  
Jamie R. Oliver ◽  
Lindsey E. Moses ◽  
Moses Tam ◽  
Zujun Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Population Based ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Median Income ◽  
Racial Groups ◽  
Hpv Status

Objective To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB). Study Design Population-based cohort study. Setting Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear. Subjects and Methods All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed. Results In total, 45,940 patients met criteria. Most were male (38,038, 82.8%), older than 60 years (23,456, 51.5%), and white (40,156, 87.4%), and lived in higher median income areas (>$48,000, 28,587, 62.2%). Two-thirds were HPV positive (31,007, 67.5%). HPV-negative disease was significantly more common in lower SES (<$38,000, 2937, 41.5%, P < .001) and among blacks (1784, 55.3%, P < .001). Median follow-up was 33 months. Five-year overall survival was 81.3% (95% CI, 80.5%-82.1%) and 59.6% (95% CI, 58.2%-61.0%) in HPV-positive and HPV-negative groups, respectively. In univariable and multivariable analyses controlling for HPV status, age, stage, and treatment, black race (hazard ratio [HR], 1.22; 95% CI, 1.11-1.34; P < .001) and low SES (HR, 1.58; 95% CI, 1.45-1.72; P < .001) were associated with worse survival. Conclusion Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.

Characteristics of the course of squamous cell carcinoma of the oral cavity depending on the HPV status.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17579-e17579
Author(s):  
Pavel V. Svetitskiy ◽  
Tatiana A. Zykova ◽  
Viktoriya L. Volkova ◽  
Irina V. Aedinova
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Lower Grade ◽  
Tumor Tissues ◽  
Hpv Status ◽  
Formalin Fixed Paraffin Embedded

e17579 Background: HPV infection has a positive prognostic value in the treatment of patients with oropharyngeal squamous cell carcinoma. The purpose of the study was to evaluate the effect of HPV status on the course of oral cavity cancer. Methods: Formalin-fixed paraffin-embedded tumor tissues were studied in 34 patients with cancer of the floor of the mouth aged 47-85 years, 3 (8.8%) women and 31 (91.2%) men. All patients had histologically verified squamous cell carcinoma: stage (st) I in 1 (2.9%), II st - 8 (23.5%), III st - 12 (35.3%), IV st - 13 (38.3%); G1 in 15 (44.1%), G2 - 19 (55.9%). HPV DNAs were detected by Real-time PCR. Results: HPV DNAs were found in 12 (35.3%) samples of tumor tissues, including type 6 in 1 (2.9%), 11 in 3 (8.8%), 16 in 6 (17.6%), 35 in 1 (2.9%), 16+35 in 1 (2.9%). HPV+ tumors were more often in women (66.7% vs 32.3% in men), but high-risk HPV types were detected in men only - 8 (25.8%). Among patients aged 47-55 years, HPV+ tumor status was detected in 4 (33.3%), 56-65 years in 7 (53.8%), 66 years and older - in 1 (11.1%). In st I, no HPV+ tumors were observed; st II - 3 (37.5%) HPV+ tumors, low-risk in all; st III - 3 (25%) HPV+ patients, including high-risk in 2 (16.7%); st IV - 6 (46.2%) HPV+ samples, high-risk in all. G1 tumors: HPV+ in 7 (46.7%), HPV- in 8 (53.3%) patients; G2 tumors: HPV+ in 5 (26.3%), HPV- in 14 (73.7%) patients. Among patients with HPV+ tumors, metastases were observed in 5 (41.7%), no metastases - in 7 (58.3%); for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. 4 (33.3%) patients with HPV+ tumors died, while 8 (66.7%) survived; for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. Conclusions: The development of squamous cell carcinoma of the oral cavity was multidirectional and depended on the HPV status. HPV+ tumors, especially high-risk ones, were more often registered in stages III and IV. HPV+ tumors were more often lower-grade ones and less often metastasized; the mortality rate among patients with HPV+ tumors was lower than with HPV- ones.

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