Abstract
Squamous papillomas (SPs) of the head and neck are generally regarded as a human papillomavirus (HPV)-driven process, but reported rates of HPV detection vary dramatically. Moreover, they are generally considered a benign condition, but the detection of high risk HPV types is commonly reported. This latter finding is particularly disturbing to clinicians and their patients given the alarming rise of HPV-associated head and neck cancer. The capriciousness of HPV detection reflects in large part differences in methodologies. The purpose of this study was to review an institutional experience using a state of the art detection method to determine the presence, type and anatomic distribution of HPV in head and neck SPs. The surgical pathology files of the Mount Sinai Hospital were reviewed for all SPs that had undergone HPV testing between 2012 and 2018. HPV screening was performed on tissue blocks with real-time PCR using primers designed to target the L1 region of low and high-risk HPV types. Genotyping was performed on HPV positive cases. HPV detection was repeated for cases that were originally reported to be positive for high risk HPV. 134 cases had undergone HPV analysis. Of the 131 with sufficient cellular material, 2 were excluded because the HPV testing yielded inconclusive results. The remaining 129 cases were the basis of this study. Thirty-eight cases (29%) were HPV positive and 91 (71%) were negative. The most common genotype was HPV 6 (n = 27, 71%), followed by HPV 11 (n = 10, 26%). One case (1%) was HPV positive but the genotype could not be determined. Of the HPV negative cases, 3 were originally reported as HPV 16 positive but found to be HPV negative on re-review and repeat testing. SPs arising in the larynx were more likely to harbor HPV than those arising in the oral cavity and oropharynx (64% vs. 10%, p < 0.00001). Similarly, recurrent respiratory papillomatosis (RRP) were much more likely to be HPV positive than solitary SPs (71% vs. 10%, p < 0.00001). Almost a third of head and neck SPs harbor HPV, but incidence is highly dependent on anatomic site. Those arising in the larynx are more prone to be HPV-driven than those arising in the oral cavity and oropharynx, particularly when occurring in the setting of RRP. High risk HPV could not be confirmed in any of the cases. Routine HPV testing as a strategy to unmask potentially malignant lesions harboring high risk HPV is not likely to be useful.
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References
Egawa N, Egawa K, Griffin H, Doorbar J. Human papillomaviruses; epithelial tropisms, and the development of neoplasia. Viruses. 2015;7(7):3863–90.
Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294–301.
Berman TA, Schiller JT. Human papillomavirus in cervical cancer and oropharyngeal cancer: one cause, two diseases. Cancer. 2017;123(12):2219–29.
Westra WH. Detection of human papillomavirus (HPV) in clinical samples: evolving methods and strategies for the accurate determination of HPV status of head and neck carcinomas. Oral Oncol. 2014;50(9):771–9.
Kansky AA, Seme K, Maver PJ, Luzar B, Gale N, Poljak M. Human papillomaviruses (HPV) in tissue specimens of oral squamous cell papillomas and normal oral mucosa. Anticancer Res. 2006;26(4B):3197–201.
Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009;125(2):362–6.
Barzal-Nowosielska M, Miasko A, Staroslawska E, Sulewska A, Chyczewski L. Detection of human papillomavirus in papillomas of oral cavity. Folia Histochem Cytobiol. 2001;39(Suppl 2):189–90.
Paparotto Lopes SM, Meeks VI. Analysis of HPV 16 and 18 by in situ hybridization in oral papilloma of HIV + patients. Gen Dent. 2001;49(4):386–9 quiz 90-1.
Soares CP, Benatti Neto C, Fregonezi PA, Teresa DB, Santos RT, Longatto Filho A, et al. Computer-assisted analysis of p53 and PCNA expression in oral lesions infected with human papillomavirus. Anal Quant Cytol Histol. 2003;25(1):19–24.
Dona MG, Pichi B, Rollo F, Gheit T, Laquintana V, Covello R, et al. Mucosal and cutaneous human papillomaviruses in head and neck squamous cell papillomas. Head Neck. 2017;39(2):254–9.
Orita Y, Gion Y, Tachibana T, Ikegami K, Marunaka H, Makihara S, et al. Laryngeal squamous cell papilloma is highly associated with human papillomavirus. Jpn J Clin Oncol. 2018;48(4):350–5.
Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014;383(9916):524–32.
Wieland U, Kreuter A. The importance of HPV16 in anal cancer prevention. Lancet Infect Dis. 2018;18(2):131–2.
Lin C, Franceschi S, Clifford GM. Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis. Lancet Infect Dis. 2018;18(2):198–206.
Lewis JS Jr, Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C, et al. Human papillomavirus testing in head and neck carcinomas: guideline from the college of American pathologists. Arch Pathol Lab Med. 2018;142(5):559–97.
de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ, Snijders PJ. The use of general primers GP5 and GP6 elongated at their 3′ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol. 1995;76(Pt 4):1057–62.
Cai YP, Yang Y, Zhu BL, Li Y, Xia XY, Zhang RF, et al. Comparison of human papillomavirus detection and genotyping with four different prime sets by PCR-sequencing. Biomed Environ Sci. 2013;26(1):40–7.
Kreimer AR, Bhatia RK, Messeguer AL, Gonzalez P, Herrero R, Giuliano AR. Oral human papillomavirus in healthy individuals: a systematic review of the literature. Sex Transm Dis. 2010;37(6):386–91.
Gillison ML, Broutian T, Pickard RK, Tong ZY, Xiao W, Kahle L, et al. Prevalence of oral HPV infection in the United States, 2009–2010. JAMA. 2012;307(7):693–703.
Martin E, Dang J, Bzhalava D, Stern J, Edelstein ZR, Koutsky LA, et al. Characterization of three novel human papillomavirus types isolated from oral rinse samples of healthy individuals. J Clin Virol. 2014;59(1):30–7.
Garbuglia AR. Human papillomavirus in head and neck cancer. Cancers (Basel). 2014;6(3):1705–26.
Tjon Pian Gi RE, San Giorgi MR, Pawlita M, Michel A, van Hemel BM, Schuuring EM, et al. Immunological response to quadrivalent HPV vaccine in treatment of recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol. 2016;273(10):3231–6.
Larson DA, Derkay CS. Epidemiology of recurrent respiratory papillomatosis. APMIS. 2010;118(6–7):450–4.
Huang CM. Human papillomavirus and vaccination. Mayo Clin Proc. 2008;83(6):701–6 quiz 6-7.
Wiatrak BJ, Wiatrak DW, Broker TR, Lewis L. Recurrent respiratory papillomatosis: a longitudinal study comparing severity associated with human papilloma viral types 6 and 11 and other risk factors in a large pediatric population. Laryngoscope. 2004;114((11 Pt 2 Suppl 104)):1–23.
Omland T, Lie KA, Akre H, Sandlie LE, Jebsen P, Sandvik L, et al. Recurrent respiratory papillomatosis: HPV genotypes and risk of high-grade laryngeal neoplasia. PLoS ONE. 2014;9(6):e99114.
Petry KU, Luyten A, Justus A, Iftner A, Strehlke S, Schulze-Rath R, et al. Prevalence of low-risk HPV types and genital warts in women born 1988/89 or 1983/84 -results of WOLVES, a population-based epidemiological study in Wolfsburg, Germany. BMC Infect Dis. 2012;12:367.
Castle PE, Hunt WC, Langsfeld E, Wheeler CM, New Mexico HPVPRSC. Three-year risk of cervical precancer and cancer after the detection of low-risk human papillomavirus genotypes targeted by a commercial test. Obstet Gynecol. 2014;123(1):49–56.
Soler C, Allibert P, Chardonnet Y, Cros P, Mandrand B, Thivolet J. Detection of human papillomavirus types 6, 11, 16 and 18 in mucosal and cutaneous lesions by the multiplex polymerase chain reaction. J Virol Methods. 1991;35(2):143–57.
Dickens P, Srivastava G, Loke SL, Larkin S. Human papillomavirus 6, 11, and 16 in laryngeal papillomas. J Pathol. 1991;165(3):243–6.
Doyle DJ, Henderson LA, LeJeune FE Jr, Miller RH. Changes in human papillomavirus typing of recurrent respiratory papillomatosis progressing to malignant neoplasm. Arch Otolaryngol Head Neck Surg. 1994;120(11):1273–6.
Pou AM, Rimell FL, Jordan JA, Shoemaker DL, Johnson JT, Barua P, et al. Adult respiratory papillomatosis: human papillomavirus type and viral coinfections as predictors of prognosis. Ann Otol Rhinol Laryngol. 1995;104(10 Pt 1):758–62.
Jimenez C, Correnti M, Salma N, Cavazza ME, Perrone M. Detection of human papillomavirus DNA in benign oral squamous epithelial lesions in Venezuela. J Oral Pathol Med. 2001;30(7):385–8.
Snietura M, Lamch R, Kopec A, Waniczek D, Likus W, Lange D, et al. Oral and oropharyngeal papillomas are not associated with high-risk human papillomavirus infection. Eur Arch Otorhinolaryngol. 2017;274(9):3477–83.
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Trzcinska, A., Zhang, W., Gitman, M. et al. The Prevalence, Anatomic Distribution and Significance of HPV Genotypes in Head and Neck Squamous Papillomas as Detected by Real-Time PCR and Sanger Sequencing. Head and Neck Pathol 14, 428–434 (2020). https://doi.org/10.1007/s12105-019-01057-7
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DOI: https://doi.org/10.1007/s12105-019-01057-7