ORIGINAL ARTICLE
Assessment of HPV16 infection in patients with laryngeal cancer
 
More details
Hide details
1
Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, Poland
 
2
Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
 
3
Department of Tumour Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, Krakow, Poland
 
4
Department of Radiotherapy for Children and Adults, University Children's Hospital of Krakow, Poland
 
5
Jagiellonian University in Krakow, Faculty of Health Sciences, Krakow, Poland
 
 
Publication date: 2021-05-31
 
 
Pol J Pathol 2021;72(1):64-74
 
KEYWORDS
ABSTRACT
The purpose of the study was to investigate HPV16 infection in laryngeal cancer patients treated with surgery and adjuvant radiotherapy as well as to analyze treatment results in relation to HPV16 infection and selected clinical, histopathological, and radiotherapy parameters.
A retrospective analysis was performed in a group of 60 patients with squamous cell carcinoma of the larynx treated surgically and qualified for adjuvant radiotherapy at the Oncology Center in Cracow between 1995 and 2001. The studied group consisted of 57 men (95%) and 3 women (5%) of mean age of 56 years. In
13 patients (22%) underweight was noted. In the analyzed material, locally advanced laryngeal cancer prevailed (pT3-pT4) – 52 cases (87%), with the involvement of cervical lymph nodes (pN+) – 32 cases (53%). Histopathological examination revealed that microscopic radicality was not obtained in 18 patients (30%). Human papillomavirus 16 infection status as well as infection type (integrated, episomal, or mixed) were assessed in each patient by means of quantitative polymerase chain reaction (qPCR) using real-time detection.
The 5-year OS, DFS, and LC rates were 45%, 61%, and 69%, respectively. Multivariate analysis revealed that local relapse risk and local failure risk were statistically significantly influenced by underweight and positive surgical margin. Underweight had also a statistically significant impact on death risk. The HPV16 infection was noticed in 4 cancers (6.8%). In all cases it was the same episomal type.
On the basis of our observations it can be assumed that HPV infection does not play an important role in etiology of laryngeal cancer. Although, further study is needed in larger patient populations; optimal methodology for detecting HPV infection should also be determined. Positive surgical margin has a significant effect on worse treatment outcomes. Underweight before radiotherapy diminishes the probability of treatment success and survival of laryngeal cancer patients.
REFERENCES (48)
1.
Didkowska J, Wojciechowska U, Olasek P. Cancer in Poland in 2015. Krajowy Rejestr nowotworów. Center of Oncology, Maria Sklodowska-Curie Institute, Warsaw 2017.
 
2.
Forastiere AA, Weber RS. Long-term results of intergroup RTOG 91-11: A phase III trial to preserve the larynx-induction cisplatin/5Fu and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy. J Clin Oncol 2001; 24 (suppl): 284. Abstract 5517.
 
3.
Hinerman RW, Morris CG, Amur MJ, et al. Surgery and postoperative radiotherapy for squamous cell carcinoma of the larynx and pharynx. Am J Clin Oncol 2006; 29: 613-621.
 
4.
Mucha-Ma³ecka A, Sk³adowski K, Lange D. Histopathological factors influencing results of combined treatment in patients with laryngeal cancer. Pol J Pathol 2015; 66: 260-268.
 
5.
Skóra T, Nowak-Sadzikowska J, Mucha-Ma³ecka A, et al. Postoperative irradiation in patients with pT3-4N0 laryngeal cancer: results and prognostic factors. Eur Arch Otorhinolaryngol 2015; 272: 673-679.
 
6.
Peters LJ, Goepfert H, Ang KK, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. Int J Radiat Oncol Biol Phys 1993; 26: 3-11.
 
7.
Warren GW, Alberg AJ, Kraft AS, et al. The 2014 Surgeon General’s report: “The health consequences of smoking – 50 years of progress”: a paradigm shift in cancer care. Cancer 2014; 120: 1914-1916.
 
8.
Syrjanen K, Syrjanen S, Pyrhonen S. Human papilloma virus (HPV) antigens in lesions of laryngeal squamous cell carcinomas. ORL J Otorhinolaryngol Relat Spec 1982; 44: 323-334.
 
9.
Meng HX, Miao SS, Chen K, et al. Association of p16 as prognostic factors for oropharyngeal cancer: Evaluation of p16 in 1470 patients for a 16 year study in Northeast China. Biomed Res Int 2018; 2018: 9594568.
 
10.
Biesaga B, Mucha-Ma³ecka A, Janecka-Wid³a A, et al. Differences in the prognosis of HPV16-positive patients with squamous cell carcinoma of head and neck according to viral load and expression of p16. J Cancer Res Clin Oncol 2018; 144: 63-73.
 
11.
Snietura M, Piglowski W, Jaworska M, et al. Impact of HPV infection on the clinical outcome of p-CAIR trial in head and neck cancer. Eur Arch Otorhinolaryngol 2011; 268: 721-726.
 
12.
Li X, Gao L, Li H, et al. Human papillomavirus infection and laryngeal cancer risk: a systematic review and meta-analysis.
 
13.
J Infect Dis 2013; 207: 479488.
 
14.
Ndiaye C, Mena M, Alemany L, et al. HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol 2014; 15: 1319-1331.
 
15.
Biesaga B, Janecka A, Mucha-Ma³ecka A, et al. HPV16 detection by qPCR method in relation to quantity and quality of DNA extracted from archival formalin fixed and paraffin embedded head and neck cancer tissues by three commercially available kits. J Virol Methods 2016; 236: 157-163.
 
16.
Si HX, Tsao SWP, Poon CS, et al. Physical status of HPV-16 in esophageal squamous cell carcinoma. J Clin Virol 2005; 32: 19-23.
 
17.
Biesaga B, Szostek S, Klimek M, et al. Comparison of the sensitivity and specificity of real-time PCR and in situ hybridization in HPV16 and 18 detection in archival cervical cancer specimens. Folia Histochem Cytobiol 2012; 50: 239-247.
 
18.
Lewis JS Jr, Chernock RD, Ma XJ, et al. Partial p16 staining in oropharyngeal squamous cell carcinoma: extent and pattern correlate with human papillomavirus RNA status. Mod Pathol 2012; 25: 1212-1220.
 
19.
Weems DH, Mendenhall WM, Parsons JT, et al. Squamous cell carcinoma of the supraglottic larynx treated with surgery and/or radiation therapy. Int J Radiat Oncol Biol Phys 1987; 13: 1483-1487.
 
20.
Mucha-Ma³ecka A, Sk³adowski K, Wygoda A, et al. Radiotherapy of locally advanced laryngeal cancer: the Gliwice Center of Oncology experience, 1990-96. Nowotwory J Oncol 2001; 51: 35-41.
 
21.
Mucha-Ma³ecka A, Sk³adowski K. High dose radiotherapy alone for patients with T-4-stage laryngeal cancer. Strahlenther Onkol 2013; 189: 632-638.
 
22.
Hoebers F, Rios E, Troost E, et al. Definitive radiation therapy for treatment of laryngeal carcinoma: impact of local relapse on outcome and implications for treatment strategies. Strahlenther Onkol 2013; 189: 834-841.
 
23.
Parsons JT, Mendenhall WM, Stringer SP, et al. An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity. Int J Radiat Oncol Biol Phys 1997; 1: 137-148.
 
24.
Ma³ecki K, Mucha-Ma³ecka A, Gliñski B, et al. Leczenie chorych na zaawansowanego raka krtani i krtaniowej czêœci gard³a z zaoszczêdzeniem narz¹du g³osu. Onkol Info 2009; 5: 163-167.
 
25.
Blanchard P, Baujat B, Holostenco V, et al. Metaanalysis of chemotherapy in head and neck cancer (MACH-NC): A comprehensive analysis by tumour site. Radiother Oncol 2011; 100: 33-40.
 
26.
Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017; 67: 93-99.
 
27.
Onerci Celebi O, Sener E, Hosal S, et al. Human papillomavirus infection in patients with laryngeal carcinoma. BMC Cancer 2018; 18: 1005.
 
28.
Duray A, Descamps G, Arafa M, et al. High incidence of high-risk HPV in benign and malignant lesions of the larynx. Int.
 
29.
J Oncol 2011; 39: 51-59.
 
30.
Torrente MC, Rodrigo JP, Haigentz M, et al. Human papillomavirus infections in laryngeal cancer. Head Neck 2011; 33: 581-586.
 
31.
de Martel C, Plummer M, Vignat J, et al. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer 2017; 141: 664-670.
 
32.
Castellsagué X, Alemany L, Quer M, et al. HPV involvement in head and neck cancers: Comprehensive assessment of biomarkers in 3680 patients. J Natl Cancer Inst 2016; 108: 403.
 
33.
Narisawa-Saito M, Kiyono T. Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins. Cancer Sci 2007; 98: 1505-1511.
 
34.
Peitsaro P, Johansson B, Syrjänen S. Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique. J Clin Microbiol 2002; 40: 886-891.
 
35.
Cheung JL, Cheung TH, Ng CW, et al. Analysis of human papillomavirus type 18 load and integration status from low-grade cervical lesion to invasive cervical cancer. J Clin Microbiol 2009; 47: 287-293.
 
36.
Fujii T, Masumoto N, Saito M, et al. Comparison between in situ hybridization and real-time PCR technique as a means of detecting the integrated form of human papillomavirus 16 in cervical neoplasia. Diagn Mol Pathol 2005; 14: 103-108.
 
37.
Saunier M, Monnier-Benoit S, Mauny F, et al. Analysis of human papillomavirus type 16 (HPV16) DNA load and physical state for identification of HPV16-infected women with high-grade lesions or cervical carcinoma. J Clin Microbiol 2008; 46: 3678-3685.
 
38.
Jiang M, Baseman JG, Koutsky LA, et al. Sequence variation of human papillomavirus type 16 and measurement of viral integration by quantitative PCR. J Clin Microbiol 2009; 47: 521-526.
 
39.
Prigge ES, Arbyn M, von Knebel Doeberitz M, et al. Diagnostic accuracy of p16 INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis. Int J Cancer 2017; 140: 1186-1198.
 
40.
Li J, Poi MJ, Tsai M-D. The regulatory mechanisms of tumor suppressor P16INK4A and relevance to cancer. Biochemistry 2011; 50: 5566-5582.
 
41.
Basheeth N, O’Leary G, Khan H, et al. Oncologic outcomes of total laryngectomy: impact of margins and preoperative tracheostomy. Head Neck 2015; 37: 862-869.
 
42.
Johnson JT, Barmes EL, Myers EN, et al. The extracapsular spread of tumors in cervical node metastasis. Arch Otolaryngol 1981; 107: 725-729.
 
43.
Saraniti C, Speciale R, Gallina S, et al. Prognostic role of resection margin in open oncologic laryngeal surgery: survival analysis of a cohort of 139 patients affected by squamous cell carcinoma. Braz J Otorhinolaryngol 2019; 85: 603-610.
 
44.
Mucha-Ma³ecka A, Chrostowska A, Urbanek K, et al. Prognostic factors in patients with T1 glottic cancer treated with radiotherapy. Strahlenther Onkol 2019; 195: 792-804.
 
45.
Hollander Dd, Kampman E, van Herpen CM. Pretreatment body mass index and head and neck cancer outcome: A review of the literature. Crit Rev Oncol Hematol 2015; 96: 328-338.
 
46.
Li ZQ, Zou L, Liu TR, Yang AK. Prognostic value of body mass index before treatment for laryngeal squamous cell carcinoma. Cancer Biol Med 2015; 12: 394-400.
 
47.
Te Riele RJLM, Dronkers EAC, Wieringa MH, et al. Influence of anemia and BMI on prognosis of laryngeal squamous cell carcinoma: Development of an updated prognostic model. Oral Oncol 2018; 78: 25-30.
 
48.
van Bokhorst-de van der Schueren MA, van Leeuwen PA, Sauerwein HP, et al. Assessment of malnutrition parameters in head and neck cancer and their relation to postoperative complications. Head Neck 1997;19:419-425.
 
eISSN:2084-9869
ISSN:1233-9687
Journals System - logo
Scroll to top