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Context Human papillomavirus (HPV) is a major cause of oropharyngeal squamous cell carcinomas, and HPV (and/or surrogate marker p16) status has emerged as a prognostic marker that significantly impacts clinical management. There is no current consensus on when to test oropharyngeal squamous cell carcinomas for HPV/p16 or on which tests to choose. Objective To develop evidence-based recommendations for the testing, application, interpretation, and reporting of HPV and surrogate marker tests in head and neck carcinomas. Design The College of American Pathologists convened a panel of experts in head and neck and molecular pathology, as well as surgical, medical, and radiation oncology, to develop recommendations. A systematic review of the literature was conducted to address 6 key questions. Final recommendations were derived from strength of evidence, open comment period feedback, and expert panel consensus. Results The major recommendations include (1) testing newly diagnosed oropharyngeal squamous cell carcinoma patients for high-risk HPV, either from the primary tumor or from cervical nodal metastases, using p16 immunohistochemistry with a 70% nuclear and cytoplasmic staining cutoff, and (2) not routinely testing nonsquamous oropharyngeal carcinomas or nonoropharyngeal carcinomas for HPV. Pathologists are to report tumors as HPV positive or p16 positive. Guidelines are provided for testing cytologic samples and handling of locoregional and distant recurrence specimens. Conclusions Based on the systematic review and on expert panel consensus, high-risk HPV testing is recommended for all new oropharyngeal squamous cell carcinoma patients, but not routinely recommended for other head and neck carcinomas.

Spot 14 (S14) is a ∼17 KD nuclear protein that functions at the transcriptional level to regulate de novo synthesis of fatty acids in liver, brown and white adipose, and. lactating mammary tissues. Localization of the S14 gene to. chromosome 11q13.5 suggested it may contribute to tumorigenes is in breast. In ∼15% of breast cancers, chromosome 11q13 is amplified and this predicts a poor prognosis. Although two candidate oncogenes from this region, CCND1 and EMS1, were identified, most studies suggest there are other cooperating oncogenes at 11q13. Overexpression of fatty acid synthase (FAS), a key lipogenic enzyme, occurs in a subset of breast cancers and also predicts a poor prognosis. Furthermore, pharmacologic inhibition of FAS in lipogenic tumors induced apoptosis. This raised the question of whether amplification of the S14 gene caused S14 overexpression and thereby stimulated tumor lipogenesis. The focus of this the.sis, was to determine whether S14 is part of the 11q13 amplicon and to characterize its potential role in the pathophysiology of breast cancer. The S14 gene was localized to between markers D11S906 and D11S937, at the telomeric end of the 11q13 amplicon and was amplified in 2/7 breast cancer cell lines. Expression of S14 was identified in 6/7 breast cancer cell lines. The cell line that did not express S14, MDA-MB-435s, was the only one with a relatively low rate of lipogenesis. Expression of S14 was also examined by immunohistochemistry. In normal breast, S14 expression only occurred when there was lactation. In 21 primary breast cancers, S14 was expressed in 67%, and acetyl-CoA carboxylase was expressed in 71%. The expression of S14 and ACC was 86% concordant. Expression of S14 was also induced by progesterone in T47D breast cancer cells. The induction occurred in close association with the degree and time course of FAS induction. These data supported the hypothesis that S14 is part of the 11q13 amplicon and that its expression causes increased tumor lipogenesis. Inhibiting S14 expression may have the same effect as pharmacologic inhibition of FAS and would therefore make S14 an excellent target for anti-neoplastic therapies.