Basaloid Squamous Cell Carcinoma of the Head and Neck is a Mixed Variant That Can be Further Resolved by HPV Status

Begum, Shanaz; Westra, William H.

doi:10.1097/pas.0b013e31816380ec

Cited by 209 publications

(212 citation statements)

References 28 publications

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“…Some studies have shown no association of HPV/p16 expression with basaloid squamous cell carcinoma, whereas other recent studies have suggested that HPV may be present and accompanied by strong p16 expression, especially in basaloid squamous cell carcinoma of the oropharynx. [22][23][24][25] It is also important to keep in mind that strong and diffuse p16 staining can occur in adenoid cystic carcinoma, even in the absence of co-existing HPV infection, and focal p16 expression is extremely common in these tumors. Lastly, although p16 overexpression is often used as a surrogate marker for HPV infection in squamous cell carcinoma, it cannot be used in this manner in high-grade adenoid cystic carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck

et al. 2012

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Squamous cell carcinoma of the head and neck, particularly basaloid squamous cell carcinoma, may be difficult to distinguish from high-grade adenoid cystic carcinoma. Evidence of human papilloma virus (HPV) infection, particularly HPV 16, is frequently found in non-keratinizing oropharyngeal squamous cell carcinoma. Immunoreactivity for p16, a surrogate marker for HPV infection, often parallels the HPV infection status in oropharyngeal squamous cell carcinoma. However, the incidence and correlation between p16 expression and HPV infection in high-grade adenoid cystic carcinoma is unknown. Sixteen cases of high-grade adenoid cystic carcinoma, three cases of dedifferentiated adenoid cystic carcinoma and eight cases of low-/intermediate-grade adenoid cystic carcinoma were identified for inclusion in the study. All cases were tested by immunohistochemistry for p16 expression and in situ hybridization for high-and low-risk HPV. Eight cases (100%) of low-to-intermediate-grade adenoid cystic carcinoma were focally positive for p16, all of which were negative for HPV. In all, 14 of 16 cases (88%) of high-grade adenoid cystic carcinoma and three cases (100%) of dedifferentiated adenoid cystic carcinoma were positive for p16; strong and diffuse staining was noted in three cases (3 of 19, 16%). Two cases (11%) of high-grade adenoid cystic carcinoma, which were also diffusely positive for p16, showed the presence of high-risk HPV. These findings suggest that the presence of HPV infection in high-grade adenoid cystic carcinoma is infrequent, even in the presence of p16 immunostaining. Nevertheless, HPV positivity should not be used to exclude the possibility of high-grade adenoid cystic carcinoma when the differential diagnosis includes squamous cell carcinoma. Moreover, although p16 overexpression is often used as a surrogate marker for HPV in squamous cell carcinoma, it cannot be used in this manner in high-grade adenoid cystic carcinoma.

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Section: Discussionmentioning

confidence: 99%

Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck

et al. 2012

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“…Although they appeared to do well clinically, the number of cases is too small to make any meaningful conclusions. Several histologic variants of SCC, including nonkeratinizing SCC, basaloid SCC, papillary SCC, and undifferentiated carcinoma [7][8][9][10], have been shown to harbor high risk HPV when arising in the oropharynx. Papillary SCC, in particular, can have transcriptionally-active HPV in nonoropharyngeal locations such as the larynx [9].…”

Section: Discussionmentioning

confidence: 99%

“…These tumors may present as different variants distinct from the typical keratinizingtype SCC, including nonkeratinizing [5,6], basaloid [7,8], and papillary SCC [9] and also undifferentiated carcinoma [10]. It has also been documented in several studies that HPV-related carcinomas of the upper aerodigestive tract have more favorable prognosis than HPV negative ones [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Adenosquamous Carcinoma of the Head and Neck: Relationship to Human Papillomavirus and Review of the Literature

Masand

El‐Mofty

et al. 2011

Head and Neck Pathol

133

106

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Adenosquamous carcinoma (ADSC) of the head and neck is an aggressive variant of squamous cell carcinoma (SCC). Certain variants of head and neck SCC are human papillomavirus (HPV)-related and have better prognosis. The relationship of HPV to head and neck ADSC has not been investigated. We searched our files for the term ''adenosquamous'' and head and neck subsites and found cases from 1998 to 2009. The requisite histologic criteria were the presence of SCC combined with distinct gland formation and/or intracellular mucin. DNA in situ hybridization for high-risk HPV, RNA in situ hybridization for high risk HPV E6 and E7 transcripts, and immunohistochemistry for p16 and p53 were performed. The existing literature on ADSC was also reviewed. Of the 18 cases, eight were from the larynx and hypopharynx, four from the oral cavity, three from the oropharynx, and three from the nasal cavity. Three cases (16%) showed both high risk HPV E6 and E7 and p16 expression, one from the nasal cavity and two from the oropharynx. Both oropharyngeal carcinoma patients were alive and disease free at 34 and 103 months, respectively. ADSCs of the head and neck are a heterogeneous group of tumors. A small minority of cases harbor HPV and most of these, particularly those occurring at sites with known high prevalence of HPV, show active viral transcription with detectable E6 and E7 and overexpression of p16. The HPV-related oropharyngeal cases, though rare, appear to do very well clinically, while the remaining cohort of ADSC patients do quite poorly. Head and neck ADSC appears to be a mixed variant that can be further classified according to its HPV status.

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“…Also, all major studies that performed multivariate survival analysis to control for other variables have found that positive p16 IHC independently correlates with better survival [2,5,6,9,12]. In particular, it is also prognostically independent of the histologic features of the SCC [22], such as keratinizing versus nonkeratinizing types (unpublished data), and, for most, if not all, specifically-defined SCC variants arising in the oropharynx, such as basaloid SCC [23], undifferentiated carcinoma [24], and adenosquamous carcinoma [25].…”

Section: Introductionmentioning

confidence: 95%

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

Lewis

2012

Head and Neck Pathol

208

197

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It is widely acknowledged that human papillomavirus (HPV)-related oropharyngeal carcinoma is a biologically unique form of head and neck cancer that should be singled out and treated differently. It is now incumbent to find a test (or combination of tests) that accurately identifies cancers with the associated favorable prognosis for proper patient counseling and management and for placing patients in the correct treatment arms in the emerging clinical trials that are attempting to establish unique treatment types and approaches. The test (or combination of tests) that are utilized must be widely available, reliable, easy to interpret, and wellvalidated. While HPV-specific testing seems completely logical to use as a single test or one of a combination of tests, it turns out to be quite complicated in practice. Because of the different forms of the virus, the differing types of HPV-specific tests can give different information. HPV DNA, RNA, and protein assays have varying sensitivities for virus detection and also varying availability from formalin-fixed, paraffin-embedded tissue. Since p16 protein over expression is very sensitive for the presence of transcriptionally-active HPV and since it correlates strongly with patient outcomes, is widely available, and easy to interpret, it appears to currently be the single test that combines all of the desired attributes in a risk stratification marker for widespread implementation in clinical and research study settings. This article will review the literature on p16 immunohistochemistry and its relation to HPV-specific testing, discuss some practical issues related to its implementation, and present the case for why it should be the single test used for this purpose.

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Basaloid Squamous Cell Carcinoma of the Head and Neck is a Mixed Variant That Can be Further Resolved by HPV Status

Cited by 209 publications

References 28 publications

Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck

Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck

Adenosquamous Carcinoma of the Head and Neck: Relationship to Human Papillomavirus and Review of the Literature

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

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