Human papillomavirus (HPV) infection interferes with DNA repair and the destruction of cells with unrepairable defective DNA. This means that mutated cells survive to become cancers, instead of being eliminated. The virus also directly disrupts the cell nucleus. HPV has been found in a proportion of laryngeal cancers, an alleged smoking-related cancer. As was the case with cervical cancer, it is likely that as methodology improves, the proportion of laryngeal cancer in which HPV is implicated will increase with time. The majority of this work has only been performed since 1996, and the US health establishment has had relatively little involvement.
The tobacco industry funded some of the pioneering investigations of Syrjanen and Syrjanen. The absence of interest and support from the health establishment accounts for their seeking support from this source. History now shows that the Syrjanens were right to suspect a role for HPV. In 1989, a research analyst for Shook, Hardy & Bacon noted that the industry position paper on cancer of the larynx ignored HPV ("The one theory of causation which is noticeably absent from Mr. Goold's paper is that of human papillomavirus (HPV) as an etiologic agent for some squamous cell carcinomas of the larynx..."). But, despite ironclad proof that the anti-smokers falsely blamed smoking for cervical cancer that was actually caused by HPV, the tobacco lawyers have never uttered so much as a word about this subject. This is conspiracy. at the Minnesota tobacco trial, the tobacco industry said nothing about HPV. For obvious reasons, neither did Jonathan Samet, the anti-smokers' star perjuror about smoking and health. Furthermore, these facts cast a whole different light on those demonstrations against the tobacco companies that the anti-smoking demagogues arranged: The anti-smokers are to blame for their misfortune, because they are the ones who obstructed the truth!
Histological evidence for the presence of condylomatous epithelial lesions in association with laryngeal squamous cell carcinoma. KJ Syrjanen, SM Syrjanen. ORL J Otorhinolaryngol Relat Spec 1981;43(4):181-194. "The role of HPV in the development of these lesions is discussed, and the possibility is raised that HPV might be the agent responsible for contributing to the development of squamous cell carcinoma of the larynx in man."Syrjanen - ORL Otorhinolaryngol Relat Spec 1981 abstract / PubMed
Analysis of prevalence of human papillomavirus in laryngeal
carcinomas. Study of 40 cases using polymerase chain reaction and
consensus primers. MS Brandwein, GJ Nuovo, H Biller. Ann Otol Rhinol
Laryngol 1993 Apr;102(4 Pt 1):309-313. 3 of 40 patients (8%) had
detectable HPV DNA, by polymerase chain reaction (PCR) with the "hot
start" modification and consensus primers that can detect over 30
distinct HPV types.
High frequency of p53 abnormality in laryngeal cancers of heavy smokers and its relation to human papillomavirus infection. T Suzuki, K Shidara, F Hara, T Nakajima. Jpn J Cancer Res 1994 Nov;85(11):1087-1093. 11/41 (27%) laryngeal cancers were positive for HPV 16/18.Suzuki - Jpn J Cancer Res 1994 abstract / PubMed
Prevalence of human papillomaviruses (HPV) in benign and
tumors of the upper respiratory tract. J Shen, JE Tate, CP Crum, ML
Goodman. Mod Pathol 1996 Jan;9(1):15-20. 3/32 (9%) laryngeal squamous
carcinomas were positive for HPV types 6 and 11.
Detection of human papillomavirus DNA in laryngeal squamous cell carcinoma by polymerase chain reaction. G Almadori, G Cadoni, P Cattani, P Posteraro, E Scarano, F Ottaviani, G Paludetti, M Maurizi. Eur J Cancer 1996 May;32A(5):783-788. Nine (20%) of 45 patients were positive, by PCR with consensus primers that detect HPV types 6, 11, 16 and 18.Almadori - Eur J Cancer 1996 abstract / PubMed
Human papillomavirus and cancers of the upper aerodigestive
review of epidemiological and experimental evidence. S Franceschi, N
Munoz, XF Bosch, PJ Snijders, JM Walboomers. Cancer Epidemiol
Biomarkers Prev 1996 Jul;5(7):567-575. "Increased risk of cancer of the
oral cavity, pharynx, and larynx subsequent to the occurrence of cancer
of the cervix has been found and suggests common etiological factors
besides smoking. HPV has been found in a substantial proportion of
benign UADT lesions, most notably laryngeal papillomas and oral
verrucal-papillary lesions. Largest and most accurate case series
(i.e., > 15 UADT cancer cases, based on best HPV detection
techniques) showed HPV DNA in 46% of cancers of the oral cavity and
pharynx, 15% of cancers of the esophagus, and 24% of cancers of the
larynx, with however, great discrepancies from one study to another."
Presence of human papillomavirus in squamous cell laryngeal
carcinomas. A study of thirty-nine cases using polymerase chain
reaction and in situ hybridization. ES Lie, F Karison, R Holm. Acta
Otolaryngol 1996 Nov;116(6):900-905. 3/39 (8%) were positive for HPV,
with specific PCR primers for HPV 6, 11, 16, 18, 31, 33 and 35 and with
in situ hybridization (ISH). One was HPV 16 and the other two " type
related to HPV 6/11."
[The detection of human papillomavirus in papillomas of the larynx and tonsils through immunohistochemistry and DNA in situ hybridization]. M Lopez Amado, T Garcia Caballero, A Lozano Ramirez, T Labella Caballero. An Otorrinolaringol Ibero Am 1997;24(3):269-280. 5/10 laryngeal papillomas were HPV-positive; two of these patients later developed a laryngeal carcinoma.Lopez Amado - An Otorrinolaringol Ibero Am 1997 abstract / PubMed
[A preliminary study on p53 gene expression and infection of
papilloma virus in laryngeal squamous cell carcinoma]. M Xie, J Xiao, Z
Tao, J Luo. Hunan I Ko Ta Hsueh Hsueh Pao 1997;22(3):209-211. 3/13
(23.1%) laryngeal squamous cell carcinomas were positive for HPV type
16; no HPV 18 reported.
[Study on the relation between HPV and tumors of the throat
larynx]. J Ren, X Wang, Q Zhu. Lin Chuong Erh Pi Yen Hou Ko Tsa Chih
1997 Apr;11(4):157-159. 6/22 (27.3%) of laryngeal squamous cell
carcinomas were positive for HPV DNA (HPV types 6, 11, 16, or 18).
[Detection of human papillomavirus gene sequences in laryngeal tumors and premalignant changes by polymerase chain reaction]. J Czegledy, T Major, A Juhasz, G Repassy, L Gergely. Orv Hetil 1997 Jul 27;138(30):1891-1895. "In the squamous cell carcinomas, papillomas and precancerous lesions the presence of human papillomavirus gene sequences was significantly higher than in the control group." (HPV types 6, 11, 16 and 18).Czegledy - Orv Hetil 1997 abstract / PubMed
Using polymerase chain reaction to human papillomavirus in
pharyngolaryngeal carcinomas. I Alvarez Alvarez, P Sanchez Lazo, S
Ramos Gonzalez, JP Rodrigo Tapia, F Nunez Batalla, C Suarez Nieto. Am J
Otolaryngol 1997 Nov-Dec;18(6):375-381. "HPV E6 DNA of the 6b and 16
types was detected in 14 patients (25%)," but not HPV 18.
Localization of p53 protein and human papillomavirus in laryngeal squamous lesions. ML Caruso, AM Valentini. Anticancer Res 1997 Nov-Dec;17(6D):4671-4675. 1/12 (8%) laryngeal squamous cell carcinomas was positive for HPV16 or 18.Caruso - Anticancer Res 1997 abstract / PubMed
[Study on HPV infection and p53 protein expression in laryngeal carcinoma]. Z Qin, M Dong. Lin Chuang Erh Pi Yen Hou Ko Tsa Chih 1997 Dec;11(12):546-549. 19/44 (43.2%) of laryngeal squamous cell carcinomas were positive for HPV 16/18.Qin - Lin Chuang Erh Pi Yen Hou Ko Tsa Chih 1997 abstract / PubMed
Low detection rate of HPV in oral and laryngeal carcinomas. T Matzow, M Boysen, M Kalantari, B Johansson, B Hagmar. Acta Oncol 1998;37(1):73-76. 3/16 (19%) laryngeal carcinomas and dysplasias were positive for HPV.Matzow - Acta Oncol 1998 abstract / PubMed
Human papillomavirus DNA sequences and p53 over-expression in laryngeal squamous cell carcinomas in Northeast China. XL Ma, K Ueno, ZM Pan, sz Hi, M Ohyama, Y Eizuru. J Med Virol 1998 Mar;54(3):186-191. 60/102 (58.8%) were positive for HPV types 16, 18, 6, 11 or 33.Ma - J Med Virol 1998 abstract / PubMed
Malignant transformation of recurrent respiratory
associated with integrated human papillomavirus type 11 DNA and
mutation of p53. PL Rady, VJ Schnadig, RL Weiss, TK Hughes, SK Tyring.
Laryngoscope 1998 May;108(5):735-740. "[T]he p53 genetic mutation was
associated with integration of HPV-11 in histologically malignant
Detection and typing of human papillomavirus DNA in benign and malignant tumours of laryngeal epithelium. R García-Milián, H Hernández, L Panadé, C Rodríguez, N González, C Valenzuela, MD Araña, SE Perea. Acta Otolaryngol 1998 Sep;118(5):754-758. "Four normal laryngeal samples (16%) were positive for HPV DNA against the 24 samples (82%) (p < 0.001) found for laryngeal papilloma and 16 (48.5%) (p < 0.05) found for laryngeal squamous cell carcinoma. HPV 16 was the type most frequently found in laryngeal carcinoma samples. Our results support an etiologic role for this type of HPV in the pathogenesis of laryngeal carcinoma."García-Milián - Acta Otolaryngol 1998 abstract / PubMed
Association between cyclin D1 (CCND1) gene amplification and human papillomavirus infection in human laryngeal squamous cell carcinoma. P Cattani, S Hohaus, A Bellacosa, M Genuardi, S Cavallo, V Rovella, G Almadori, G Cadoni, J Galli, M Maurizi, G Fadda, G Neri. Clin Cancer Res 1998 Nov;4(11):2585-2589. "HPV DNA was detected in 22 of 75 (29.3%) tumors, and it belonged almost exclusively to the highly oncogenic HPV-16, HPV-18, and HPV-33."Cattani - Clin Cancer Res 1998 abstract / PubMed
Human papilloma virus (HPV) type 16 and 18 detected in head and neck squamous cell carcinoma. H Mineta, T Ogino, HM Amano, Y Ohkawa, K Araki, S Takebayashi, K Miura. Anticancer Res 1998 Nov-Dec;18(6B):4765-4768. 10/26 (38%) laryngeal squamous cell carcinomas were positive for HPV16/18.Mineta - Anticancer Res 1998 abstract / PubMed
Human papilloma virus (HPV) is possibly involved in laryngeal but not in lung carcinogenesis. VG Gorgoulis, P Zacharatos, A Kotsinas, A Kyroudi, AN Rassidakis, JA Ikonomopoulos, C Barbatis, CS Herrington, C Kittas. Hum Pathol 1999 Mar;30(3):274-283. HPV DNA was found in 19/91 (21%) laryngeal squamous cell carcinomas.Gorgoulis - Hum Pathol 1999 abstract / PubMed
Detection of human papillomavirus (HPV) in laryngeal carcinoma lines provides evidence for a heterogeneic cell population. S Atula, R Grenman, H Kujari, S Syrjanen. Eur J Cancer 1999 May;35(5):825-832. 7/27 (26%) cell lines and 7/12 (58%) tumor samples were positive for high-risk types of HPV.Atula - Eur J Cancer 1999 abstract / PubMed
Demonstration of multiple HPV types in laryngeal premalignant lesions using polymerase chain reaction and immunohistochemistry. B Azzimonti, L Hertel, P Aluffi, F Pia, G Monga, M Zocchi, S Landolfo, M Gariglio. J Med Virol 1999 Sep;59(1):110-116. "The presence of HPV DNA was detected in 28 of 50 specimens (56%), including 9/12 cases with mild dysplasia (75%), 3/6 cases with moderate dysplasia (50%), and 7/11 cases with severe dysplasia (64%). Multiple HPV infections, containing two or three types, were detected in 17 of the 28 HPV-positive lesions (60%). Of 21 cases with keratosis and no dysplasia, 11 were positive for HPV DNA (52%) and 4 showed L1 staining (36%). By contrast, L1 positivity was revealed only in two lesions with moderate dysplasia, confirming that fully productive HPV infection is strictly dependent on epithelial differentiation and surface keratinization. The probability that HPV is a cofactor in the malignant progression of these lesions is suggested by the fact that 3/4 patients who developed cancer within 50 months were positive for HPV DNA."Azzimonti - J Med Virol 1999 abstract / PubMed
Laryngeal cancer and human papillomavirus: HPV is absent in
majority of laryngeal carcinomas. H Lindeberg, A Krogdahl. Cancer Lett
1999 Nov 1;146(1):9-13. 1/30 laryngeal carcinomas from patients without
pre-existing recurrent laryngeal papillomatosis were HPV+. "The HPV
type present could not be determined, but it was not type 6, 11, 13,
16, 18, 30, 31, 33, 35 or 45."
Human papillomavirus in head and neck carcinomas: prevalence, physical status and relationship with clinical/pathological parameters. G Badaracco, A Venuti, R Morello, A Muller, ML Marcante. Anticancer Res 2000 Mar-Apr;20(2B):1301-1305. Of 66 tumors from various sites including 22 laryngeal squamous cell carcinomas, 24 were HPV-positive. "HPV 16 was integrated in 7/12 positive tumours without site-specificity. HPV infection was not related to age, gender, tumour stage, differentiation grade, and use of alcohol and/or tobacco."Badaracco - Anticancer Res 2000 abstract / PubMed
Physical state and expression of human papillomavirus in laryngeal carcinoma and surrounding normal mucosa. A Venuti, V Manni, R Morello, F De Marco, F Marzetti, ML Marcante. J Med Virol 2000 Apr;60(4):396-402. 13/25 (52%) were HPV-positive: 7 for HPV-16, 5 for HPV-6, and 1 for HPV-45.Venuti - J Med Virol 2000 abstract / PubMed
[Human papillomavirus (HPV) in the laryngeal carcinoma]. W Makowska, M Malejczyk, D Kapiszewska, J Nyckowska, E Wojcikiewicz, B Wroblewska. Otolaryngol Pol 2001;55(3):263-266. 10/23 (43.5%) were positive for HPV.Makowska - Otolaryngol Pol 2001 abstract / PubMed
Prevalence of human papillomavirus (HPV) DNA in larynx and
carcinomas. H Kaya, E Kotlioglu, S Inanli, G Ekicioglu, SU Bozkurt, A
Tutkun, S Kullu. Pathologica 2001 Oct;93(5):531-534. 10/21 (47.6%)
laryngeal SCCs were positive for HPV. "Typing showed signals of HPV
6/11, 16/18 and 31/33 infection in 80%, 40%, 30% of the laryngeal
Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. JP Klussmann, SJ Weissenborn, U Wieland, V Dries, J Kolligs, M Jungehuelsing, HE Eckel, HP Dienes, HJ Pfister, PG Fuchs. Cancer 2001 Dec 1;92(11):2875-2884. "Altogether 25 HNSCCs (26%) were found to be HPV positive. Stratified according to the tumor localization, the frequency of HPV positive lesions was 18% in the oral cavity, 45% for oropharynx, 25% for hypopharynx, 8% for nasopharynx, and 7% for larynx. The highest HPV DNA prevalence (58%) was found in tonsillar carcinomas."Klussmann - Cancer 2001 abstract / PubMed
Human papillomavirus infection and epidermal growth factor
expression in primary laryngeal squamous cell carcinoma. G Almadori, G
Cadoni, P Cattani, J Galli, F Bussu, G Ferrandina, G Scambia, G Fadda,
M Maurizi. Clin Cancer Res 2001 Dec;7(12):3988-3993. HPV DNA was found
in 15/42 (35.7%), nearly all of high-risk types HPV-16, HPV-18, and
HPV-33. "At analysis by Mann-Whitney nonparametric statistical test,
EGFR level was found to be significantly higher in HPV-infected than in
HPV-negative cases (T = 440; P = 0.002). EGFR overexpression
(EGFR-positive status >6 fmol/mg protein, the arbitrary cutoff
chosen) was found in 20 of 42 (47.6%) tumors, and it was associated
with HPV infection in a statistically significant extent (2 = 4.686; P
= 0.03). Conclusions: Viral oncoproteins have been shown to induce a
perturbation of the cell response to signals for growth and
differentiation; these findings confirm that enhanced EGFR expression
and activation in laryngeal squamous cell carcinoma may occur also as a
consequence of HPV infection and support the hypothesis of an
involvement of HPV infection in laryngeal carcinogenesis."
[Causal association between human papilloma virus infection
and neck and esophageal squamous cell carcinoma]. Z Szentirmay, I
Szántó, I Bálint, K Pólus, E
Remenár, L Tamás, G Szentkúti, Z Melegh, P
Nagy, M Kásler. Magy Onkol 2002;46(1):35-41. "Overall, HPV
were detected in 61 of 150 specimens. HPV DNA sequences were detected
in 16/32 specimens in the oropharyngeal region, in 13/36 specimens in
larynx and 32/82 specimens in esophagus. Papillomas contained only the
episomal form of HPV 16. In the esophagus, the most common type was HPV
73. In all specimens examined, HPV 6/11 (4/150), HPV 16 (23/150), HPV
35 (1/150), HPV 45 (1/150), HPV 54 (1/150), HPV 58 (1/150), HPV 61
(1/150), HPV 66 (1/150), HPV 68 (2/150), HPV 70 (3/150), HPV 72
(1/150), HPV 73 (16/150), double HPV infection (2/150), and
unidentified HPV type (4/150) was detected. Interestingly, HPV was
found in all verrucous carcinomas and in 18/22 basaloid squamous cell
Cellular manifestations of human papillomavirus infection in laryngeal tissues. SE Jacob, S Sreevidya, E Chacko, MR Pillai. J Surg Oncol 2002 Mar;79(3):142-150. 15/44 (34%) invasive cancers were HPV positive.Jacob - J Surg Oncol 2002 abstract / PubMed
Human papillomavirus-positive tonsillar carcinomas: a
tumor entity? JP Klussmann, SJ Weissenborn, U Wieland, V Dries, HE
Eckel, HJ Pfister, PG Fuchs. Med Microbiol Immunol (Berl) 2003
Aug;192(3):129-132. 25% of hypopharyngeal cancers and 7% of
laryngeal cancers were HPV DNA positive.
Prevalence of human papillomavirus type 16 DNA in squamous
carcinoma of the palatine tonsil, and not the oral cavity, in young
patients: a distinct clinicopathologic and molecular disease entity. SK
El-Mofty, DW Lu. Am J Surg Pathol 2003 Nov;27(11):1463-1470. In 33
patients under the age of 40 years, HPV DNA was detected by polymerase
chain reaction in 0/15 oral, 10/11 tonsillar, and 2/7 laryngeal tumors.
11/12 HPV-positive tumors were HPV16 and 1 was HPV31.
A systematic review of case-control studies of human
infection in laryngeal squamous cell carcinoma. L Rees, M Birchall, M
Bailey, S Thomas. Clin Otolaryngol Allied Sci 2004 Aug;29(4):301-306.
Review. "The studies are heterogeneous in the methods used to harvest
tissue samples and techniques for detecting the virus within the
tissue. HPV-16 positivity among cases ranged from 2.7% to 46.9% and
0-5.7% among controls. Two studies showed a significantly increased
risk of LSCC if HPV-16 was present (OR 18.5, 95% CI 2.2-154.8, OR 2.6,
95% CI 1.1-6.0)."
Integration of human papillomavirus type 11 in recurrent
papilloma-associated cancer. PM Reidy, HH Dedo, R Rabah, JB Field, RH
Mathog, L Gregoire, WD Lancaster. Laryngoscope 2004
Nov;114(11):1906-1909. "HPV-11 but not HPV-6, 16, or 18 was found in
all of the laryngeal and bronchogenic cancers in patients with a
history of early onset RRP in this study... HPV type 6 and 11 are
considered "low-risk" viruses and are not associated with genital
cancers, as are HPV types 16 and 18. However, our data suggests that
HPV type 11 is an aggressive virus in laryngeal papilloma that should
be monitored in patients with RRP."
Altered patterns of the interferon-inducible gene IFI16
in head and neck squamous cell carcinoma: immunohistochemical study
including correlation with retinoblastoma protein, human papillomavirus
infection and proliferation index. B Azzimonti, M Pagano, M Mondini, M
De Andrea, G Valente, G Monga, M Tommasino, P Aluffi, S Landolfo, M
Gariglio. Histopathology 2004 Dec;45(6):560-572. "HPV DNA was found in
14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC
High co-prevalence of genogroup 1 TT virus and human
is associated with poor clinical outcome of laryngeal carcinoma. G
Szladek, A Juhasz, G Kardos, K Szoke, T Major, I Sziklai, I Tar, I
Marton, J Konya, L Gergely, K Szarka. J Clin Pathol 2005
Apr;58(4):402-405. 40 healthy individuals, 10 patients with recurrent
papillomatosis, five patients with papillomatosis with malignant
transformation, and 25 patients with laryngeal carcinoma. "In the 11
patients with carcinoma who had metastasis or relapse there was a high
rate of coinfection with genogroup 1 TTV and HPV (eight of 11), whereas
in the 14 without tumour progression no coinfection was found.
Coinfection was associated with significantly lower tumour free
survival in patients with carcinoma (p < 0.001). Furthermore,
of five patients who had papillomatosis with malignant transformation
were coinfected with genogroup 1 TTV and HPV."
Molecular detection and typing of human papillomavirus in
carcinoma specimens. MC Torrente, S Ampuero, M Abud, JM Ojeda. Acta
Otolaryngol 2005 Aug;125(8):888-893. "Ten of the 31 samples (32%) were
positive for HPV DNA and all of the samples were positive for human
beta-globin. The genotypes identified were HPV 16 (n=3), HPV 58 (n=2)
and HPV 39, 45, 51, 59, 66 and 69 (n=1 for each). The three samples
positive for HPV 16 had lost region E2, meaning that the viral DNA had
been integrated into the host genome."
[The prevalence of E6/E7 HPV type 16 in laryngeal cancer and
normal mucosa] K Morshed, M Polz-Dacewicz, B Rajtar, M Szymanski, M
Ziaja-Soltys, W Golabek. Pol Merkur Lekarski 2005 Sep;19(111):291-293.
HPV 16 DNA was found in 26 (36.1%) of 72 samples of laryngeal squamous
Immunohistochemical demonstration of multiple HPV types in
squamous cell carcinoma. K Morshed, E Korobowicz, M Szymanski, D
Skomra, W Golabek. Eur Arch Otorhinolaryngol 2005 Nov;262(11):917-920.
6/40 (15%) of laryngeal squamous cell carcinoma patients were positive
for HPV, versus zero of 33 controls with with non-neoplastic laryngeal
lesions or laryngeal nodules. "Five (83.4%) of six patients with HPV
positive tumors had G2 (moderately differentiated), one patient (16.6%)
had G3 (poorly differentiated), and no patient with HPV positive tumor
had a G1 (well-differentiated) tumor. Four (66.6%) of the six HPV
positive tumors were in the supraglottic region, one (16.6%) tumor was
located in the glottis, and one (16.6%) HPV positive tumor was in the
Human papillomavirus and head and neck cancer: a systematic
and meta-analysis. CG Hobbs, JA Sterne, M Bailey, RS Heyderman, MA
Birchall, SJ Thomas. Clin Otolaryngol 2006 Aug;31(4):259-266. "The
association between HPV16 and cancer was strongest for tonsil (OR:
15.1, 95% CI: 6.8-33.7), intermediate for oropharynx (OR: 4.3, 95% CI:
2.1-8.9) and weakest for oral (OR: 2.0, 95% CI: 1.2-3.4) and larynx
(OR: 2.0, 95% CI: 1.0-4.2). To investigate heterogeneity, further
stratification by method of HPV16 detection, suggested that variation
in the magnitude of the HPV-cancer association with cancer site was
restricted to studies using ELISA: among studies using PCR, the
magnitude of the summary odds ratios was similar across the four sites."
Human papillomavirus and Epstein-Barr virus infection, p53
expression, and cellular proliferation in laryngeal carcinoma. DE de
Oliveira, MM Bacchi, RS Macarenco, JV Tagliarini, RC Cordeiro, CE
Bacchi. Am J Clin Pathol 2006 Aug;126(2):284-293. In 110 squamous cell
carcinomas of the larynx, "High-grade HPV was found in 37.3% of cases,
and none had demonstrable EBV infection."
Wart Virus Linked to Head and Neck Squamous Cell Carcinoma:
Presented at AHNS. By John Otrompke. Doctor's Guide, Aug. 22, 2006.
Presentation title: Frequency and Types of Human Papilloma Virus in
Head and neck Squamous Cell Carcinoma. Poster 160,presented at the 2006
annual meeting of the American Head and Neck Society (AHNS), by
Jose-Francisco Gallegos-Hernandez. In 118 head and neck cancer
patients, HPV was found in 42% of the
cases, 70% of which were HPV16. "Fifty percent of patients with
laryngeal cancer had HPV, he said. HPV type 16 was present in 20% of
those with mouth cancer, 25% of those with cancer of the mucosae, and
66% of those with cancer of the palate, while no other forms of HPV
were found in patients with those forms of cancer in the study, the
poster said. HPV was found more frequently in patients over 50 years of
age and in men."
Detection of human papillomavirus and relevant tumor
oncoproteins in laryngeal tumors. ME Manjarrez, R Ocadiz, L Valle, C
Pacheco, A Marroquin, C De la Torre, M Selman, P Gariglio. Clin Cancer
Res 2006 Dec 1;12(23):6946-6951. 16 laryngeal carcinomas versus 13
individuals who died of nonmalignant causes. "Most laryngeal
papillomatosis samples contained low-risk HPV determined by both
techniques. However, 25% of laryngeal carcinoma samples were positive
for HPV employing PCR or in situ PCR." "In laryngeal cancer, we found
that in situ PCR was more sensitive than in vitro PCR, detecting
HPV-DNA in 25% of the samples as compared with 12.5% when in vitro PCR
was employed. The large difference in the percentages reported by other
authors can be explained partly by the different detection methods
used." "Two cases with laryngeal cancer showed high-risk and low-risk
HPV whereas the other two contained either low-risk HPV or high-risk
HPV, suggesting that both low-risk and high-risk HPV might be involved
in the development of laryngeal malignant tumors in a subset of
patients, and that these viruses may be a synergistic risk factor for
malignant development." Low-risk HPV was present in all papillomatosis
[Human papillomavirus: association with head and neck cancer.]
Gallegos-Hernández, E Paredes-Hernández, R
Flores-Díaz, G Minauro-Muñoz, T Apresa-García, DM
Hernández-Hernández. Cir Cir 2007 May-Jun;75(3):151-155.
"Results: There were 118 patients were HPV positive and oropharyngeal
and laryngeal cancer patients were the most frequently affected (55%
and 50%, respectively). HPV-16 was most frequently isolated (70%).
Laryngeal cancer patients suffered the highest ratio of HPV-16
infection (68.7%). Factors associated with HPV (univariate analysis)
were age >50 years, tobacco/alcohol consumption and male gender.
multivariate analysis, none of the variables showed importance (p
>0.5); HPV infection was more frequent in patients with history
alcohol/tobacco consumption (p = 0.6)."
Human papilloma virus prevalence in laryngeal squamous cell
carcinoma. A Gungor, H Cincik, H Baloglu, E Cekin, S Dogru, E
Dursun. J Laryngol Otol 2007 Aug;121(8):772-774. "Human papilloma
virus deoxyribonucleic acid was detected in seven of 95 cases of
laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma
virus genotyping revealed double human papilloma virus infection in
three cases and single human papilloma virus infection in the remaining
four cases. The human papilloma virus genotypes detected were 6, 11 and
16 (the latter detected in only one case)."
Alcohol, smoking and human papillomavirus in laryngeal
Nordic prospective multicenter study. WJ Koskinen, K Brøndbo, H
Mellin Dahlstrand, T Luostarinen, T Hakulinen, I Leivo, A Molijn, WG
Quint, T Røysland, E Munck-Wikland, AA Mäkitie, I
Pyykkö, J Dillner, A Vaheri, LM Aaltonen. J Cancer Res Clin Oncol
2007 Sep;133(9):673-678. Fresh-frozen laryngeal cancer biopsies from
108 patients in Finland, Norway, and Sweden. Four (3.3%) were positive
for HPV, type(s) not specified in abstract.
Lack of association of alcohol and tobacco with
head and neck cancer. KM Applebaum, CS Furniss, A Zeka, MR Posner, JF
Smith, J Bryan, EA Eisen, ES Peters, MD McClean, KT Kelsey. J Natl
Cancer Inst 2007 Dec 5;99(23):1801-1810. 485 cases (93 laryngeal
tumors) and 549 controls. 80.7% of laryngeal cancer patients were
negative for HPV16 by serology, which is neither reliable nor complete.
Four of the authors were from the Harvard School of Public Health, and
it was funded by the National Institutes of Health.
High incidence of malignant transformation of laryngeal
Taiwan. LA Lee, AJ Cheng, TJ Fang, CG Huang, CT Liao, JT Chang, HY Li.
Laryngoscope 2008 Jan;118(1):50-55. 26 consecutive laryngeal papilloma
patients. "During 237 person-years of follow-up, six new,
pathologically confirmed cases of laryngeal carcinoma were ascertained
(incidence 2.5/100 person-years), and all were associated with HPV-6 or
HPV-11. Malignant transformation revealed no correlation with the
following: age less than 3 years at diagnosis, sex, history of tobacco
use, history of alcohol consumption, family history of laryngeal
cancer, or type of laryngeal papilloma. Laryngeal papilloma without
demonstrable HPV DNA was the only significant risk factor for malignant
transformation (P < .05). The cumulative risk of malignant
transformation in subjects without demonstrable HPV DNA was
significantly higher than that in HPV-positive patients (relative risk,
8.0; 95% confidence interval, 1.1-60.3; P = .05)."
Short-fragment PCR assay for highly sensitive broad-spectrum
detection of human papillomaviruses in laryngeal squamous cell
carcinoma and normal mucosa: clinico-pathological evaluation. K
Morshed, M Polz-Dacewicz, M Szymański, D Polz. Eur Arch
Otorhinolaryngol 2008 Jul;265 Suppl 1:S89-96. 93 primary laryngeal
squamous cell carcinomas, 49 specimens of normal mucosa, and 22
specimens of laryngeal nodules serving as controls. By SPF(10) HPV DNA
test, PCR/DEIA method and INNO-LiPA genotyping assay, "Human
papillomavirus was detected in 33 (35.5%) of the 93 samples from LSCC,
in 4 (8.2%) of 49 samples of the normal mucosa and it was not detected
in any of the sample from the control group. Twenty-eight of 33 (81.8%)
were positive for HPV-16, 6 of 33 (18.2%) were positive for HPV-18 and
5 of 33 (15.1%) were positive for HPV-33. Multiple infection was found
in 5 of 33 (15.1%); 3 samples were positive for HPV-16 and HPV-33, 2
samples for HPV-16 and HPV-18." "The difference between the presence of
HPV in squamous cell carcinoma tumors and in control group samples was
statistically significant (χ2 = 8.13; P =
between the presence of HPV in squamous cell carcinoma tumors and in
normal mucosa from the surgical margin in patients with LSCC samples
was statistically significant (χ2 = 3.78; P =
Table 1, 32.5%
of carcinomas in smokers were HPV-positive, versus 36.4% in non-smokers
(P = 0.48).
Retraction: WITHDRAWN: Human papillomavirus detection and
in squamous cell
carcinomas of the larynx. AM Silva, CA Vilanova-Costa, SF de Oliveira,
CC da Silva, MP Curado, AD da Cruz. J Virol Methods 2009
In 20 cases, "HPV DNA was amplified in 25% of cases,
and the amplified products from the first PCR were genotyped using
specific primers for HPVs 6, 11, 16, 18, 33, 35, 45 and 58. HPV33
genome was found in three samples and HPV45 in two samples as the viral
types associated most frequently with laryngeal cancer. HPVs 11, 16,
and 18 were also genotyped. Three patients had two viral types
simultaneously, suggesting that co-infection may play an important role
in the etiology of cancer of the larynx."
Detection of HHV-8 and HPV in laryngeal carcinoma. MG
Güvenç, K Midilli, A Ozdoğan, E Inci, R Tahamiler, O Enver,
G Sirin, S Ergin, M Kuşkucu, EO Divanoğlu, G Yilmaz, K Altas. Auris
Nasus Larynx 2008 Sep;35(3):357-362. 47 squamous cell carcinomas (SCC)
and 3 verrucous carcinomas. "HPV DNA was detected in seven patients
(7/50; 14%) (5 out of 47 patients with SCC (5/47; 10.6%) and two out of
three patients with verrucous carcinoma). HHV-8 DNA was detected in
five patients and they all had SCC (5/47; 10.6%). One case had both
HHV-8 and HPV DNA. None of the control samples from cadavers harbored
HHV-8 DNA, or HPV DNA. There was a statistically significant
correlation between HHV-8 DNA and HPV DNA positivity and laryngeal SCC
(Fisher exact test; p=0.023 for each). No statistically significant
correlations were found between the presence of HHV-8 and/or HPV and
age, gender, tumor stage, differentiation, the site of the tumor,
smoking and alcohol use."
Use of in situ hybridization to detect human papillomavirus in
and neck squamous cell carcinoma patients without a history of alcohol
or tobacco use. WT Lee, RR Tubbs, AM Teker, J Scharpf, M Strome, B
Wood, RR Lorenz, J Hunt. Arch Pathol Lab Med 2008
Oct;132(10):1653-1656. 22 patients who did not use alcohol or tobacco,
14 male, 8 female; tongue (n = 8), tonsil (n = 7), and larynx (n = 7).
"Only 2 cases were positive for high-risk HPV, and both demonstrated an
integrated pattern. Both cases were tumors of the tonsil. No cases were
positive for low-risk HPV."
Galectin-3 overexpression in invasive laryngeal carcinoma,
by computer-assisted analysis. FA Miranda, MK Hassumi, MC
Guimarães, RT Simões, TG Silva, RC Lira, AM Rocha, CT
Mendes Jr, EA Donadi, CP Soares, EG Soares. J Histochem Cytochem 2009
Jul;57(7):665-673. "[P]araffin-embedded larynx biopsies from 65
patients, 10 in situ laryngeal carcinomas, 27 laryngeal carcinomas
without metastases, and 28 with metastases. Twenty-eight cervical lymph
nodes from patients with metastatic lesions were also evaluated." 7
(12.7%) out of 55 patients were HPV positive.
Human papillomavirus in early laryngeal carcinoma. JL Baumann,
Cohen, AN Evjen, JH Law, S Vadivelu, A Attia, JS Schindler, CH Chung,
PS Wirth, CJ Meijer, PJ Snijders, WG Yarbrough, RJ Slebos. Laryngoscope
2009 Aug;119(8):1531-1537. 38 cases of T1 or carcinoma in situ
(CIS) laryngeal lesions by PCR for 37 HPV subtypes. "HPV DNA was
detected in 6 (16%) of the 38 lesions, representing HPV types 16, 26,
31, 39, and 52,... This HPV prevalence is higher than that noted in
many previous laryngeal cancer studies, possibly due to the relatively
large panel of subtypes screened for in this study."
Papillary squamous cell carcinoma of the head and neck:
association with human papillomavirus infection and invasive carcinoma.
VY Jo, SE Mills, MH Stoler, EB Stelow. Am J Surg Pathol 2009
Nov;33(11):1720-1724. 33% of laryngeal tumors were HPV-positive by ISH.
Prevalence of high-risk human papillomavirus types (HPV-16,
and their physical status in primary laryngeal squamous cell carcinoma.
B Liu, Z Lu, P Wang, Z Basang, X Rao. Neoplasma 2010;57(6):594-600.
"Using HPV L1 general primer amplification, HPV DNA was detected in 23
(27.4%) of the 84 LSCC samples. When PCR products were cloned and
sequenced, HPV16 were found in all 23 L1 positive samples. However,
when specific primers for HPV- 16 or -18 were used to amplify E6 and E7
in all samples, 29 cases (34.5%) were positive for HPV-16, while 6
cases (7.1%) were positive for HPV 18. Coinfection of HPV-16 and -18
were found in 4 cases (4.8%). In addition, qRT-PCR assay found that
HPV-16 was characterized as episomal in 51.7% of cases, mixed (i.e.,
episomal and integrated) in 34.5%, and integrated in 13.8%, while
HPV-18 was similarly characterized as episomal in 83.3% of cases and
mixed in 16.7%. In the present study, about 36.9% of patients with LSCC
were found to be infected with HPV-16 and -18 and integration of HPV-16
and -18 DNA into the host genome was found."
Usefulness and efficiency of formalin-fixed paraffin-embedded
specimens from laryngeal squamous cell carcinoma in HPV detection by
IHC and PCR/DEIA. K Morshed, M Polz-Dacewicz, M Szymański, A Smoleń.
Folia Histochem Cytobiol 2010 Sep 30;48(3):398-402. "HPV was detected
by two methods (SPF10 PCR/DEIA and IHC) in 14 (25.92%) out of 54
specimens from FFPE. Significant differences were found between the HPV
detection using PCR/DEIA method and IHC method in FFPE tissues. The
comparative analysis of the 54 samples after assuming PCR method in
FFPE tissues showed accuracy of 92.6%, sensitivity of 90.5% and
specificity of 93.9%."
Detection of novel Human papilloma virus type 82 in laryngeal
cancer: case report. G Pannone, F Sanguedolce, A Santoro, P Fierro, M
Panetti, D Fierro, F Maiello, S De Maria, A Giannattasio, R Serpico, L
Lo Muzio, S Metafora, P Bufo. Auris Nasus Larynx 2010
Oct;37(5):648-650. "We report the case of a 51-year-old man affected by
laryngeal squamous cell carcinoma; analysis of DNA extracted by cancer
cells by an innovative molecular virology assay (INNO-LiPA HPV
Genotyping Extra) showed the presence of two high-risk HPV genotypes,
HPV-73 and -82. Immunohistochemical examination confirmed positivity
for both capsid protein and viral oncogenic protein E7."
Human papillomavirus infections in laryngeal cancer. MC
Rodrigo, M Haigentz Jr, FG Dikkers, A Rinaldo, RP Takes, J Olofsson, A
Ferlito. Head Neck 2011 Apr;33(4):581-586. Review. "[A]pproximately 25%
of laryngeal squamous cell carcinomas harbor HPV infections on
meta-analysis, with common involvement of high-risk HPV types 16
(highest frequency) and 18. Preliminary results suggest that these
high-risk HPV infections seem to be biologically relevant in laryngeal
carcinogenesis, manifested as having viral DNA integration in the
cancer cell genome and increased expression of the p16 protein."
Low human papillomavirus prevalence in head and neck cancer:
from two large case-control studies in high-incidence regions. KB
Ribeiro, JE Levi, M Pawlita, S Koifman, E Matos, J Eluf-Neto, V
Wunsch-Filho, MP Curado, O Shangina, D Zaridze, N Szeszenia-Dabrowska,
J Lissowska, A Daudt, A Menezes, V Bencko, D Mates, L Fernandez, E
Fabianova, T Gheit, M Tommasino, P Boffetta, P Brennan, T Waterboer.
Int J Epidemiol 2011 Apr;40(2):489-502. From two separate
populations, in Central Europe and Latin America. "HPV16 E7 DNA
prevalence among cases was 3.1% (6/196), including 4.4% in the
oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among
50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7
antibodies was associated with a very high risk of oropharyngeal cancer
(OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer
(OR = 14.9, 95% CI 2.92-76.1)."
Human Papillomavirus Outcomes in an Access-to-Care Laryngeal
Cohort. JK Stephen, KM Chen, V Shah, S Havard, M Lu, VP Schweitzer, G
Gardner, MJ Worsham. Otolaryngol Head Neck Surg 2012
May;146(5):730-738. 79 patients with primary LSCC. HPV16 was detected
in 27% of
LSCC patients. There were no differences in survival between
HPV-positive and HPV-negative patients.
Possible implication of Mdm2 as a prognostic marker in
laryngeal carcinoma. MK Hassumi-Fukasawa, FA Miranda-Camargo, MC
Guimarães, RT Simões, EA Donadi, CP Soares, EG Soares.
Eur Arch Otorhinolaryngol 2012 Jul;269(7):1795-1804. 7 (13.2%)
out of 53 patients were positive for HPV 6, 11, 16, 18, 31 or 33 by PCR.
Human Papillomavirus Infection and Laryngeal Cancer Risk: A systematic review and meta-analysis. X Li, H Li, J Gao, Y Yang, F Zhou, C Gao, M Li, Q Jin, L Gao. J Infect Dis 2013 Feb 1;207(3):479-488. 55 eligible studies. "The overall HPV prevalence in laryngeal cancer tissues was 28.0% (95% confidence interval [CI], 23.5%-32.9%). There were 26.6% laryngeal cancer patients were infected with high-risk types only, and HPV-16 was most frequently observed with a prevalence of 19.8% (95% CI, 15.7%-24.6%). The meta-analysis based on 12 eligible case-control studies suggests a strong association between HPV infection and laryngeal squamous cell carcinoma with a summarized odds ratio (OR) of 5.39 (95% CI, 3.25-8.94). Different magnitude of the association was observed for HPV-16 (OR=6.07, 95% CI: 3.44-10.70) and HPV-18 (OR=4.16, 95% CI: 0.87-20.04) (p<0.01)."Li - J Infect Dis 2013 abstract / PubMed
[Analysis of the human papillomavirus in laryngeal squamous cell carcinoma patients]. W Wei, YT Song, BY Zhang, JY Sun, C Chen, NS Zhang, XP Dong, Q Shi. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2013 Feb;27(1):22-24. 64 clinical diagnosed laryngeal squamous cell carcinoma patients. "In the 64 cases, 7 were positive for HPV infection by Luminex and PCR tests. 18 were positive for HPV16/18 E6 protein expression. The total positive rate was about 39. 1%."Wei - Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2013 abstract / PubMed
The role of human papillomavirus in head and neck cancer in Senegal. C Ndiaye, L Alemany, Y Diop, N Ndiaye, MJ Diémé, S Tous, JE Klaustermeier, M Alejo, X Castellsagué, FX Bosch, H Trottier, S Sanjosé. Infect Agent Cancer 2013 Apr 17;8(1):14. 3 of 25 (8.6%) laryngeal cancers were positive for HPV (Table 2).Ndiaye - Infect Agent Cancer 2013 full article / PubMed Central
Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma. G Halec, D Holzinger, M Schmitt, C Flechtenmacher, G Dyckhoff, B Lloveras, D Höfler, FX Bosch, M Pawlita. Br J Cancer 2013 Jul 9;109(1):172-183. 102 patients. "Ninety-two patients were valid in DNA analysis, of which 32 (35%) had at least one HPV DNA+ sample. Among the 29 single infections, 22 (76%) were HPV16, 2 (7%) HPV56 and 1 each (4%) HPV45, HPV53, HPV70, HPV11 and HPV42. Three cases harboured HPV16 with HPV33 (twice) or HPV45. Only 32% of HPV DNA+ findings were reproducible. Among HPV16 DNA+ L-SCC, 2 out of 23 (9%) had high viral loads, 5 out of 25 (21%) expressed E6*I mRNA and 3 out of 21 (14%) showed high p16(INK4a) and low pRb expression (all three HPV16 RNA-positive)..."Halec - Br J Cancer 2013 abstract / PubMed
Correlation of histology, human papillomavirus, and viral load
laryngeal papillomas of childhood. G Sharma, J DeHart, GJ Nuovo. Diagn
Mol Pathol 2005 Dec;14(4):230-236. 29 of 47 (62%) of cases were
positive for HPV, types 6 and 11, by ISH. There were less than 20
HPV-positive cells per tissue. 38 of 47 (81%) were positive by RT in
situ PCR using primers specific for HPVs 6 and 11, in lesions negative
P16INK4A immunostaining is a strong indicator for high-risk-HPV-associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low-risk-HPV-infection in head and neck papillomas and laryngeal dysplasias. JJ Mooren, SE Gültekin, JM Straetmans, A Haesevoets, CJ Peutz-Kootstra, CU Huebbers, HP Dienes, U Wieland, FC Ramaekers, B Kremer, EJ Speel, JP Klussmann. Int J Cancer 2013 Oct 11 [Epub ahead of print]. Paraffin-embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC), 14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal papillomas. "P16INK4A immunohistochemistry revealed a strong nuclear and cytoplasmic staining in 50 out of 51 HPV16-positive and 5 out of 111 HPV-negative OPSCC (p<0.0001) and in all HPV16-positive tonsillar dysplasias, whereas highly variable staining patterns were detected in the papillomas and laryngeal dysplasias, irrespective of the HPV-status."Mooren - Int J Cancer 2013 abstract / PubMed
Laryngeal zoster mimicking a laryngeal cancer. E Higuchi, Y
Nakamaru, R Ohwatari, T Sakashita, Y Mesuda, A Homma, Y Furuta, S
Fukuda. Otolaryngol Head and Neck Surgery 2005 Oct;133(4):1-3. The
had a white ulcerated lesion on the left arytenoid and the epiglottis,
and paralysis of the left vocal cord. Pathological
examination showed "moderate to severe dysplasia highly suggestive of
squamous cell carcinoma. However, severe inflammation precluded
definitive pathological diagnosis, and rebiopsy was recommended. At
this point, the most likely diagnosis was thought to be cancer of
Confounding By Infection
- why studies that don't include full detection of HPV (and other
causal infections) are defective, and falsely blame smoking and other
The Lie That p53 Mutations
Are the Mechanism
Behind Lung Cancer - this is because p53 mutations happen
maligancy has occurred, and the point is relevant to other cancers as