Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists

Lewis, James S.; Beadle, Beth M.; Bishop, Justin A.; Chernock, Rebecca D.; Colasacco, Carol; Lacchetti, Christina; Moncur, Joel T.; Rocco, James W.; Schwartz, Mary R.; Seethala, Raja R.; Thomas, Nicole; Westra, William H.; Faquin, William C.

doi:10.5858/arpa.2017-0286-cp

Cited by 461 publications

(558 citation statements)

References 231 publications

(217 reference statements)

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“…[27][28][29] However, for HPV analysis, only p16 immunochemistry is recommended in the eighth edition of the AJCC TNM classification. [27][28][29] However, for HPV analysis, only p16 immunochemistry is recommended in the eighth edition of the AJCC TNM classification.…”

Section: Discussionmentioning

confidence: 99%

Impact of human papillomavirus status on survival and recurrence in a geographic region with a low prevalence of HPV‐related cancer: A retrospective cohort study

et al. 2019

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Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with better tumor-response rates and survival outcomes. However, in some geographic regions, the impact of HPV infection on prognosis remains unclear. The aim of this study was to describe the patterns of recurrence and survival among patients treated for OPSCC in a geographic region with a reported low prevalence of HPV-related OPSCC. Methods: We retrospectively evaluated 215 patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to IV OPSCC who were treated with upfront surgery or radiation therapy with or without chemotherapy in a tertiary Cancer Center in Brazil. The collected data included demographic information, HPV status, tobacco and alcohol consumption, and pathologic and treatment variables. The patterns of recurrence were recorded according to HPV status. Disease-specific survival and recurrencefree survival were calculated. Results: One hundred twenty-seven (59.1%) patients were diagnosed with HPVpositive OPSCC. According to the AJCC eighth edition, 34 (15.8%), 71 (33%), 47 (21.9%), and 60 (27.9%) patients had stage I, II, III, and IV disease, respectively. Surgery was performed in 109 (50.7%) cases, and upfront chemoradiation regimens were provided in 104 (48.4%, P = .69) patients. Overall, the 5-year cancer-specific survival was 73.5% and 68.1% for patients positive and negative to HPV, respectively. Tobacco status was considered the only independent prognostic factor for survival. Furthermore, HPV status was not associated with differences in recurrence rates (P = .68). While all distant relapses were found to be lung metastases in the HPV-negative group, we observed unusual sites of distant metastases in the HPV-positive group. Conclusions: HPV status was not associated with higher rates of survival among the investigated population. Moreover, smoking status was considered the only independent prognostic factor for survival. Furthermore, patients with HPVpositive tumors were more likely than patients with HPV-negative OPSCC to have unusual distant metastases.

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Section: Discussionmentioning

confidence: 99%

Impact of human papillomavirus status on survival and recurrence in a geographic region with a low prevalence of HPV‐related cancer: A retrospective cohort study

et al. 2019

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“…It needs to be stressed that positive p16 by immunostaining is a surrogate marker of oncogenic HPV infection, and only HPV-specific tests provide definitive evidence [4,11,21]. Recently Bishop et al [22] found that the HPV-PCR (Hybrid Capture II) test correlated with p16 immunohistochemistry and HR-HPV in situ hybridization using FNA specimens.…”

Section: Resultsmentioning

confidence: 99%

“…Most OPHPVSCC are small in size but often present initially with a large cystic lymph node metastasis [2][3][4]. It has a better prognosis than human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (SCC) [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Inactivation of Rb leads to accumulation of the p16 protein, which can be detected by immunostaining in cytologic or surgical specimens [10,11]. Recently the College of American Pathologists (CAP) recommended that HR HPV testing should be performed on all patients with newly diagnosed OPHPVSCC, and p16 immunostaining can be used as a surrogate marker [4]. Although in surgical pathology specimens nuclear and cytoplasmic staining for p16 in > 70% of tumor cells is regarded as positive, the interpretation of p16 immunostaining in FNA specimens has been controversial [4].…”

Section: Introductionmentioning

confidence: 99%

“…Recently the College of American Pathologists (CAP) recommended that HR HPV testing should be performed on all patients with newly diagnosed OPHPVSCC, and p16 immunostaining can be used as a surrogate marker [4]. Although in surgical pathology specimens nuclear and cytoplasmic staining for p16 in > 70% of tumor cells is regarded as positive, the interpretation of p16 immunostaining in FNA specimens has been controversial [4]. A range from any cytoplasmic and nuclear staining to 70% staining has been used to define positivity [8,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Degenerated Keratinized Tumor Cells in Oropharyngeal Human Papilloma Virus-Associated Squamous Cell Carcinoma: A Pitfall in p16 Immunostaining of Fine-Needle Aspiration Specimens

Wei¹,

Ehya²

2018

Acta Cytologica

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Objective: High-risk human papilloma virus (HPV) testing should be performed on all patients with newly diagnosed oropharyngeal HPV-associated squamous cell carcinoma (OPHPVSCC), and p16 immunostaining can be used as a surrogate marker. Although in surgical pathology specimens p16 staining in > 70% of the tumor cells is considered a positive result, the interpretation in fine-needle aspiration (FNA) specimens has remained controversial. Study Design: FNA of neck lymph nodes and corresponding surgical specimens from 42 patients with OPHPVSCC were reviewed. Results: In FNA specimens, 38 cases (90.5%) had viable tumor cells, 32 (76.2%) had keratin debris, and 36 (85.7%) had degenerated keratinized tumor cells. Twenty-seven of 27 (100%) had positive p16 staining in > 70% of viable tumor cells, while the degenerated tumor cells were negative. Twenty of 24 (83.3%) primary OPHPVSCC exhibited focal degenerated keratinized tumor cells and/or keratin debris. Conclusions: This study showed that the majority of the OPHPVSCC metastases in lymph nodes had degenerated keratinized tumor cells and keratin debris. Many primary OPHPVSCC also demonstrated focal keratinization and/or degeneration. The degenerated tumor cells showed no immunoreactivity to p16. The same 70% cutoff used in histologic specimens should be applied in cytologic specimens, but only the viable tumor cells should be counted.

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Association of Oral Human Papillomavirus DNA Persistence With Cancer Progression After Primary Treatment for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

et al. 2019

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IMPORTANCE Detection of persistent oral human papillomavirus (HPV) DNA may be associated with recurrence of HPV-positive head and neck squamous cell carcinoma (HNSCC).OBJECTIVE To evaluate the dynamics of oral HPV DNA detection and associations with disease outcomes in patients with HPV-positive and HPV-negative HNSCC. DESIGN, SETTING, AND PARTICIPANTSThis prospective, 2-institution, tertiary referral center study of 396 patients with newly diagnosed oral cavity or oropharyngeal HNSCC was performed from July 11, 2011, to May 7, 2016. Oral rinse samples were prospectively collected at diagnosis and at completion of primary therapy. Weekly oral rinse samples were collected during radiotherapy. Purified tumor and oral rinse sample DNA were evaluated for 37 HPV types, and viral load was quantified by type-specific real-time polymerase chain reaction. Cancers were stratified by tumor HPV status, and HPV was classified as tumor type if identical to that detected in the tumor or nontumor type. MAIN OUTCOMES AND MEASURES Prevalence of HPV DNA before, during, and after therapy. Associations between tumor-type and nontumor-type oral HPV DNA detection and recurrence-free and overall survival were evaluated. RESULTS Of the 396 patients (median age, 59 years [range, 19-96 years]; 295 [74.5%] men; and 354 [89.4%] white race/ethnicity), 217 had oropharyngeal cancer; 170, oral cavity cancer; and 9, unknown primary HNSCC. The prevalence of oral HPV detection at diagnosis was higher among patients with HPV-positive compared with HPV-negative HNSCC (24 of 194 [84.2%] vs 170 of 202 [12.4%]; P < .001). Oral HPV-16 DNA had an 81% sensitivity and 100% specificity for HPV-16-positive HNSCC. The prevalence and load of tumor-type HPV decreased significantly during primary therapy with odds ratio for probability of infection with each increasing month after diagnosis (0.41; 95% CI, 0.33-0.52; P < .001), whereas those of nontumor types did not (1.01; 95% CI, 0.97-1.06; P = .62). Current smoking was significantly associated with a reduced clearance of tumor-type HPV DNA (hazard ratio [HR], 0.54; 95% CI, 0.32-0.93). Two-year overall survival was significantly lower among the HPV-positive patients with persistent detection of tumor-type HPV after therapy than among those without detectable tumor-type DNA after therapy (68% vs 95%; adjusted HR, 6.61; 95% CI, 1.86-23.44; P = .003), as was recurrence-free survival (55% vs 88%; adjusted HR, 3.72; 95% CI, 1.71-8.09; P < .001). No associations were observed for nontumor type HPV DNA among patients with HPV-positive or HPV-negative HNSCC. CONCLUSIONS AND RELEVANCEPrevalence and viral load of tumor-type HPV DNA decreased rapidly with therapy, and persistent detection was associated with increased risk of recurrence and death. Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression.

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Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists

Cited by 461 publications

References 231 publications

Impact of human papillomavirus status on survival and recurrence in a geographic region with a low prevalence of HPV‐related cancer: A retrospective cohort study

Impact of human papillomavirus status on survival and recurrence in a geographic region with a low prevalence of HPV‐related cancer: A retrospective cohort study

Degenerated Keratinized Tumor Cells in Oropharyngeal Human Papilloma Virus-Associated Squamous Cell Carcinoma: A Pitfall in p16 Immunostaining of Fine-Needle Aspiration Specimens

Association of Oral Human Papillomavirus DNA Persistence With Cancer Progression After Primary Treatment for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

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