Abstract
Human papillomavirus (HPV) infection is emerging as a major prognostic and predictive marker in head and neck squamous cell carcinoma (HNSCC). Researches are focused on the development of HPV detection assays specially designed for HNSCC. The HPV diagnosis in these tumours is relevant toprognosis even in an already-developed tumour, whereas in the cervix, where the HPV is the cause of almost all tumours, this information has less clinical relevance. The better outcome of HPV-associated HNSCC raises the question about the best methodologies to distinguish between HPV and non-HPV-associated SCC. However, no consensus has been reached on the optimal way to identify HPV-associated SCC and ancillary studies have utilised many different methodologies, including HPV polymerase chain reaction testing, HPV in situ hybridization analysis, immunohistochemical staining for p16, and newer techniques that are currently under investigation. The objective of this review is to explain and give examples of various techniques of HPV detection highlighting how they might be used clinically. Although currently insufficiently specific due to the possibility of HPV infection originating at other sites, methodologies utilising serum and plasma to measure HPV infection will also be described, mostly for their potential future development and use. Finally, DNA/RNA microarray platforms will be briefly summarized for their capacity to identify the profile of molecular changes in any particular HPV+/HPV− cancer. In this way, it is expected to be possible to correlate the appropriate transcriptome-based diagnosis to the patients’ specific cancer risk.
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References
Syrjänen KJ, Pyrhönen S, Syrjänen SM, et al. Immunohistochemical demonstration of human papilloma virus (HPV) antigens in oral squamous cell lesions. Br J Oral Surg. 1983;21:147–53.
Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.
Venuti A, Manni V, Morello R, et al. Physical state and expression of human papillomavirus in laryngeal carcinoma and surrounding normal mucosa. J Med Virol. 2000;60:396–402.
Yeudall WA, Campo MS. Human papillomavirus DNA in biopsies of oral tissues. J Gen Virol. 1991;72:173–6.
Nuovo GJ. In situ detection of human papillomavirus DNA after PCR-amplification. Methods Mol Biol. 2011;688:35–46.
Agoston ES, Robinson SJ, Mehra KK, et al. Polymerase chain reaction detection of HPV in squamous carcinoma of the oropharynx. Am J Clin Pathol. 2010;134:36–41.
Snijders PJ, Heideman DA, Meijer CJ. Methods for HPV detection in exfoliated cell and tissue specimens. APMIS 2010;118:520–8 (Review).
Gheit T, Landi S, Gemignani F, et al. Development of a sensitive and specific assay combining multiplex PCR and DNA microarray primer extension to detect high-risk mucosal human papillomavirus types. J Clin Microbiol. 2006;44:2025–31.
Remmerbach TW, Brinckmann UG, Hemprich A, et al. PCR detection of human papillomavirus of the mucosa: comparison between MY09/11 and GP5+/6+ primer sets. J Clin Virol. 2004;30:302–8.
Schmitt M, Bravo IG, Snijders PJ, et al. Bead-based multiplex genotyping of human papillomaviruses. J Clin Microbiol. 2006;44:504–12.
Smeets SJ, Hesselink AT, Speel EJ, et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer. 2007;121:2465–72.
Badaracco G, Venuti A, Morello R, et al. Human papillomavirus in head and neck carcinomas: prevalence, physical status and relationship with clinical/pathological parameters. Anticancer Res. 2000;20:1301–5.
Badaracco G, Rizzo C, Mafera B, et al. Molecular analyses and prognostic relevance of HPV in head and neck tumours. Oncol Rep. 2007;17:931–9.
Mellin H, Dahlgren L, Munck-Wikland E, et al. Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer. Int J Cancer. 2002;102:152–8.
Molden T, Kraus I, Skomedal H, et al. PreTect HPV-Proofer: real-time detection and typing of E6/E7 mRNA from carcinogenic human papillomaviruses. J Virol Methods. 2007;142:204–12.
Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29:4294–301.
Ukpo OC, Flanagan JJ, Ma XJ, et al. High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. Am J Surg Pathol. 2011;35:1343–50.
Bishop JA, Maleki Z, Valsamakis A, et al. Application of the hybrid capture 2 assay to squamous cell carcinomas of the head and neck: a convenient liquid-phase approach for the reliable determination of human papillomavirus status. Cancer Cytopathol. 2011 Jul 12. Epub ahead of print]).
Lidqvist M, Nilsson O, Holmgren J, et al. Detection of human papillomavirus oncoprotein E7 in Liquid-based cytology using monoclonal antibodies. J Gen Virol. 2011; Oct 19 [Epub ahead of print].
Chen PC, Pan CC, Kuo C, et al. Risk of oral nonmalignant lesions associated with human papillomavirus infection, betel quid chewing, and cigarette smoking in Taiwan: an integrated molecular and epidemiologic study. Arch Pathol Lab Med. 2006;130:57–61.
Lewis S Jr, Thorstad WL, Chernock RD, et al. P16 positive oropharyngeal squamous cell carcinoma: an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34:1088–96.
Thavaraj S, Stokes A, Guerra E, et al. Evaluation of human papillomavirus testing for squamous cell carcinoma of the tonsil in clinical practice. J Clin Pathol. 2011;64:308–12.
Harris SL, Thorne LB, Seaman WT, et al. Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue. Head Neck. 2010; Dec 28 [Epub ahead of print].
Martinez I, Wang J, Hobson KF, et al. Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer. 2007;43:415–32.
Mork J, Lie AK, Glattre E, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001;344:1125–31.
Anderson KS, Wong J, D’Souza G, et al. Serum antibodies to the HPV16 proteome as biomarkers for head and neck cancer. Br J Cancer. 2011;104:1896–905.
Di Lonardo A, Marcante ML, Poggiali F, et al. HPV 16 E7 antibody levels in cervical cancer patients: before and after treatment. J Med Virol. 1998;54:192–5.
Rubenstein LM, Smith EM, Pawlita M, et al. Human papillomavirus serologic follow-up response and relationship to survival in head and neck cancer: a case-comparison study. Infect Agent Cancer. 2011;6:9.
Le QT, Jones CD, Yau TK, et al. A comparison study of different PCR assays in measuring circulating plasma Epstein-Barr virus DNA levels in patients with nasopharyngeal carcinoma. Clin Cancer Res. 2005;11:5700–7.
Capone RB, Pai SI, Koch WM, et al. Detection and quantitation of human papillomavirus (HPV) DNA in the sera of patients with HPVassociated head and neck squamous cell carcinoma. Clin Cancer Res. 2000;6:4171–5.
Fakhry C, Rosenthal BT, Clark DP, et al. Associations between oral HPV16 infection and cytopathology: evaluation of an oropharyngeal “pap-test equivalent” in high-risk populations. Cancer Prev Res (Phila). 2011;4:1378–84.
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Work partially supported by a grant from the Italian Ministry of Health.
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Venuti, A., Paolini, F. HPV Detection Methods in Head and Neck Cancer. Head and Neck Pathol 6 (Suppl 1), 63–74 (2012). https://doi.org/10.1007/s12105-012-0372-5
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DOI: https://doi.org/10.1007/s12105-012-0372-5