HPV Causes Sinonasal Cancer

Association of DNA aneuploidy with human papillomavirus-induced malignant transformation of sinonasal transitional papillomas. PJ Klemi, H Joensuu, L Siivonen, E Virolainen, S Syrjänen, K Syrjänen. Otolaryngol Head Neck Surg 1989 Jun;100(6):563-567. 19 transitional papillomas of the sinonasal region and 9 maxillary squamous cell carcinomas. "Thirteen (68%) of the papillomas and none of the carcinomas contained HPV genome. Six (32%) of the papillomas and 4 (44%) of the carcinomas had an aneuploid DNA content. The relative DNA content (DNA index) of the aneuploid maxillary carcinomas was larger than that of aneuploid papillomas (p = 0.004). Three of the papillomas underwent malignant transformation, all three of which contained HPV type 16 DNA; two were also aneuploid. Data indicate that papillomas containing HPV type 16 DNA have a tendency (p = 0.06) to undergo malignant transformation, and that this tendency is greater if DNA aneuploidy or HPV type 11 DNA is also present (p = 0.02)."

Sinonasal papillomas and human papillomavirus: human papillomavirus 11 detected in fungiform Schneiderian papillomas by in situ hybridization and the polymerase chain reaction. R Judd, SR Zaki, LM Coffield, BL Evatt. Hum Pathol 1991 Jun;22(6):550-556. Four squamous papillomas, three fungiform papillomas, nine inverted papillomas, and three cylindrical cell papillomas. "All three fungiform papillomas were positive by all three techniques: immunohistochemistry, in situ hybridization for HPV 6/11, and the polymerase chain reaction for HPV 11. None of the other lesions contained detectable HPV using the specific probes included in this study."

Human papillomavirus type 6 detected by the polymerase chain reaction in invasive sinonasal papillary squamous cell carcinoma. R Judd, SR Zaki, LM Coffield, BL Evatt. Arch Pathol Lab Med 1991 Nov;115(11):1150-1153. One adenocarcinoma, two undifferentiated nasopharyngeal carcinomas, and five squamous cell carcinomas were negative for HPV infection by in situ hybridization, while a single invasive papillary squamous cell carcinoma of the maxillary sinus was positive for HPV-6.

Sinonasal Schneiderian papillomas: human papillomavirus typing by polymerase chain reaction. FH Sarkar, DW Visscher, EB Kintanar, RJ Zarbo, JD Crissman. Mod Pathol 1992 May;5(3):329-332. "The HPV gene sequences (E6-E7 portions) were not detected in any of the 24 inverted or nine cylindrical cell papillomas. One of the [two] fungiform papillomas was positive for HPV 6b/11."

Prevalence of human papillomavirus in sinonasal papillomas: a study using polymerase chain reaction and in situ hybridization. CM McLachlin, RA Kandel, TJ Colgan, DB Swanson, IJ Witterick, BY Ngan. Mod Pathol 1992 Jul;5(4):406-409. "Three of 15 inverted papillomas and two of five fungiform papillomas were positive for HPV 6/11 by ISH, whereas PCR detected HPV 6/11 sequences in two of 15 inverted and three of five fungiform papillomas. Biopsies from two patients who had serial resections contained HPV 6/11 in the original lesions and all recurrences. No HPV was detected in the carcinomas by ISH, whereas PCR detected HPV 16 in one carcinoma."

Human papillomavirus in sinonasal papillomas and squamous cell carcinoma. HK Kashima, T Kessis, RH Hruban, TC Wu, SJ Zinreich, KV Shah. Laryngoscope 1992 Sep;102(9):973-976. "Four (15%) of 26 squamous papillomas, 7 (24%) of 29 inverted papillomas, and 1 (4%) of 24 squamous carcinomas were positive for HPV when examined using the PCR amplification technique. Human papillomavirus 6 was present in 5 specimens (3 squamous and 2 inverted papillomas); HPV-11 was present in 6 specimens (1 squamous and 5 inverted papillomas); and HPV-18 was present in 1 of 24 squamous carcinomas. HPV-16 was not identified in any specimen."

Human papillomavirus (HPV) in sinonasal papillomas: a study of 78 cases using in situ hybridization and polymerase chain reaction. C Buchwald, MB Franzmann, GK Jacobsen, H Lindeberg. Laryngoscope 1995 Jan;105(1):66-71. "In only 6% of the 52 benign inverted papillomas was HPV DNA identified, whereas 69% of the exophytic papillomas were infected by HPV DNA. In none of the 5 cases with columnar cell papillomas could HPV be demonstrated. HPV 6/11 was identified in all of these HPV-positive cases. In the carcinoma area, HPV was detected in 2 (1 HPV 6/11 and 1 HPV 18) of the 5 inverted papillomas associated with carcinomas."

A majority of inverted sinonasal papillomas carries Epstein-Barr virus genomes. MR Macdonald, KT Le, J Freeman, MF Hui, RK Cheung, HM Dosch. Cancer 1995 May 1;75(9):2307-2312. "EBV DNA was found in 13 of 20 IP specimens (65%) and none of the 10 control tissues. Nine of the 20 specimens contained HPV DNA, and 5 of 20 specimens contained both EBV and HPV." HPV types 6, 11, 16, and 18 were sought.

Human papillomavirus and Epstein-Barr virus in sinonasal Schneiderian papillomas. An in situ hybridization and polymerase chain reaction study. MJ Gaffey, HF Frierson, LM Weiss, CM Barber, GB Baber, MH Stoler. Am J Clin Pathol 1996 Oct;106(4):475-482. "Polymerase chain reaction was successful in 19 papillomas, including 12 of 19 inverted SNP, 1 of 1 inverted SNP with squamous cell carcinoma, 4 of 5 fungiform SNP, and 2 of 3 oncocytic lesions. Southern blot hybridization of PCR products showed the presence of EBV DNA in two lesions, including one inverted SNP and the single inverted SNP with squamous cell carcinoma. By both DNA- and RNA-mRNA ISH, positivity for EBER was detected in rare stomal lymphocytes but not the overlying epithelium in the inverted SNP with SCC. The remaining cases, including the other inverted SNP positive for EBV by PCR, were completely negative by both ISH techniques. Human papillomavirus was detected by ISH in 1 of 19 (5%) inverted, 1 of 1 (100%) inverted with squamous cancer, 5 of 5 (100%) fungiform, and 0 of 3 (0%) oncocytic SNP. Three SNP contained HPV 6 (all fungiform), three SNP labeled for HPV 11 (two fungiform and the inverted SNP with squamous cancer), and one inverted SNP contained HPV 16."

Carcinomas occurring in papillomas of the nasal septum associated with human papilloma virus (HPV). C Buchwald, MB Franzmann, GK Jacobsen, BR Juhl, H Lindeberg. Rhinology 1997 Jun;35(2):74-78. "In the first case HPV type 6/11 was demonstrated by in-situ hybridisation and PCR in the original papilloma as well as in the recurrent papilloma and in the carcinoma. In the second case HPV type 18 was found in the nasal lesion as well as in the metastasis. All samples were examined for Epstein-Barr virus (EBV) by PCR, but with negative results."

Identification of p53 and human papilloma virus in Schneiderian papillomas. N Mirza, K Montone, Y Sato, H Kroger, DW Kennedy. Laryngoscope 1998 Apr;108(4 Pt 1):497-501. HPV was detected in six (20%) of 30 Schneiderian papillomas, "an unusual neoplasm with the propensity for local tissue destruction, recurrence, and malignant degeneration.... In the presence of HPV the odds ratio for carcinoma was 11.5:1, or 11.5 times higher than expected."

Detection of human papillomavirus (HPV) in sinonasal inverted papillomas using polymerase chain reaction (PCR). CS Hwang, HS Yang, MK Hong. Am J Rhinol 1998 Sep-Oct;12(5):363-366. "Two cases of HPV 11 and one of HPV 6 were amplified in 36 samples of benign inverted papilloma, and two cases of HPV 16 were amplified in five samples of inverted papilloma with co-existing squamous cell carcinoma."

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. "HPV16-DNA was detected in 23% of all cases (23/98), 31% (8/26) larynx, 16% (3/19) nasal and paranasal sinus, 19% (3/16) hypopharynx, 21% (3/14) oral cavity, 38% (5/13) oropharynx, and 10% (1/10) nasopharynx. HPV18-DNA was detected in 4% of all cases (4/98), 8% (2/26) larynx, and 15% (2/13) oropharynx. 54% (7/13) in oropharynx and 38% (10/26) in larynx showed rather high prevalence in the head and neck. CONCLUSIONS: HPV16 and 18 play an important role in carcinogenesis of the head and neck, especially, in the oropharynx and larynx."

Detection of human papilloma virus and Epstein-Barr virus DNA in nasopharyngeal carcinoma by polymerase chain reaction. YC Tung, KH Lin, PY Chu, CC Hsu, WR Kuo. Kao Hsiang I Hsueh Ko Hsueh Tsa Chih 1999 May;15(5):256-262. In 88 NPC tissue samples, "HPV and EBV DNA were detected in 51% and in 83% of the specimens, respectively. Coexistence of EBV and HPV in NPC was found in 42% of the samples. The "high risk" types including HPV-16 and HPV-18 accounted for 67% of 45 HPV positive samples. Furthermore, 80% of HPV-16 or HPV-18 positive samples also contained EBV DNA."

Down-regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions. M Saegusa, H Nitta, M Hashimura, I Okayasu. Histopathology 1999 Jul;35(1):55-64. HPV DNAs for type 16 and 18 were detected in two (7.4%) of 27 exophytic papillomas, six (35.8%) of 28 inverted papillomas, and nine (28.1%) of 32 squamous cell carcinomas.

Papillary squamous cell carcinomas of the upper aerodigestive tract: a clinicopathologic and molecular study. PA Suarez, K Adler-Storthz, MA Luna, AK El-Naggar, FW Abdul-Karim, JG Batsakis. Head Neck 2000 Jul;22(4):360-368. "HPV was found in 4 of 14 assessable carcinomas by in-situ hybridization and in 5 of 14 by polymerase chain reaction. The most frequently identified HPVs were HPVs in 6/11 and 16/18 patients." Some were from sites other than the sinonasal tract.

[Detection of Epstein-Barr virus and human papillomavirus in sinonasal malignant neoplasms]. PF Gao, WX Chen, LY Xiao, XJ Yan. Lin Chuang Er Bi Yan Hou Ke Za Zhi 2000 Aug;14(8):347-348. EBV was detected in 12(37.5%), HPV in 21(65.6%) of32 sinonasal malignant neoplasms [types not specified in abstract].

Human papilloma virus and p53 expression in carcinomas associated with sinonasal papillomas: a Danish Epidemiological study 1980-1998. C Buchwald, H Lindeberg, BL Pedersen, MB Franzmann. Laryngoscope 2001 Jun;111(6):1104-1110. "Among 30 examined cases of carcinomas associated with inverted papillomas, 4 cases were HPV-positive (13%).... Among the 5 carcinomas associated with exophytic papillomas, HPV was demonstrated together with p53 overexpression in 3 cases (60%)."

Significance of human papillomavirus in sinonasal papillomas. M Kraft, D Simmen, R Casas, M Pfaltz. J Laryngol Otol 2001 Sep;115(9):709-714. "HPV was detected in four of 37 specimens (11 per cent) both by ISH and PCR. In particular, HPV-11 was found in three lesions (two EP, one IP) (eight per cent), and HPV-6b was detected in one lesion (one EP) (three per cent)."

Patterns of p21(waf1/cip1) expression in non-papillomatous nasal mucosa, endophytic sinonasal papillomas, and associated carcinomas. MJ Schwerer, A Sailer, K Kraft, K Baczako, H Maier. J Clin Pathol 2001 Nov;54(11):871-876. HPV infection was found in 16 of 20 inverted papillomas, and 2 of 5 squamous cell carcinomas.

HPV infections in benign and malignant sinonasal lesions. Syrjänen KJ. J Clin Pathol 2003;56:174–81. Review. "To date, 33.3% of sinonasal papillomas and 21.7% of sinonasal carcinomas analysed have been shown to be positive for HPV. Many elements of the data parallel the observations made in HPV lesions at other mucosal sites, such as malignant transformation and frequent recurrence after radical treatment; the fact that low risk HPV types 6 and 11 are usually confined to benign lesions, whereas the reverse is true for the oncogenic HPV types 16 and 18; and the presence of squamo–columnar junctions and squamous cell metaplasia in the sinonasal system. The discrepancies reported by several studies might result in part from technical reasons, but it is also possible that sinonasal lesions have a heterogeneous aetiology (HPV related and non-related) and/or that some novel (yet unidentified) HPV types exist in these lesions, which are detected by some studies but not by others."

Human papillomavirus (HPV) in head and neck cancer. S Syrjanen. J Clin Virol 2005 Mar;32 Suppl 1:S59-66. Review. "To date, 1041 sino-nasal papillomas have been analysed for HPV and 347 (33%) cases have been positive, whereas of the 322 sino-nasal carcinomas analysed so far, 70 (22%) have been positive for any HPV type."

Human papillomavirus (HPV) transcripts in malignant inverted papilloma are from integrated HPV DNA. SP McKay, L Gregoire, F Lonardo, P Reidy, RH Mathog, WD Lancaster. Laryngoscope 2005 Aug;115(8):1428-1431. "HPV sequences were detected in samples from 3 of the 14 patients with IP [nasal inverted papilloma]. Of the three patients with SCC, HPV sequences were detected in two patients, whereas one patient was negative for the oligoprobes tested. Of the 11 patients diagnosed only with IP, 1 patient was positive for HPV DNA (HPV type 11).... and the relative level of E7 to E5 transcripts indicates integration of the viral genome. These findings are suggestive of HPV having an active role in the lesion."

Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity. SK El-Mofty, DW Lu. Am J Surg Pathol 2005 Oct;29(10):1367-1372. "HPV DNA, particularly type 16, was detected in 9 cases: 4 of 21 (19%) of [keratinizing squamous cell carcinoma], 4 of 8 (50%) of [nonkeratinizing (cylindrical cell) carcinoma], and 1 of 10 (10%) of [sinonasal undifferentiated carcinoma]."

Markers of malignant transformation of sinonasal inverted papilloma. H Katori, A Nozawa, M Tsukuda. Eur J Surg Oncol 2005 Oct;31(8):905-911. Among 44 patients with sinonasal papilloma and invasive SCC, "HPV 6/11-positive was present in 42% tumour and HPV 16/18-positive was present in 31% of tumours," by ISH.

Detection of human papillomavirus DNA in benign and malignant sinonasal neoplasms. M Hoffmann, N Klose, S Gottschlich, T Görögh, A Fazel, C Lohrey, W Rittgen, P Ambrosch, E Schwarz, T Kahn. Cancer Lett 2006 Jul 28;239(1):64-70. "To determine whether HPV DNA detection in different entities of the upper aerodigestive tract represents a coincidental, persistent/latent or specific infection, 20 clinically intact mucosa specimens of the upper aerodigestive tract, 20 sinonasal polyps, 26 inverted papillomas, and 20 squamous cell carcinomas of the paranasal sinuses were investigated. HPV DNA was not detectable in specimens derived from clinically intact mucosa or in nasal polyps. Yet, three out of 26 inverted papillomas were HPV-positive, each showing double infection with HPV6 and 11. Four out of 20 squamous cell carcinomas were HPV16 positive."

[Relationship between the biological behavior of nasal cavity or sinonasal inverted papilloma and infection of human papillomavirus]. SS Lu, JW Xu, KT Huang, QH Liao. Zhonghua Yi Xue Za Zhi 2007 May 22;87(19):1342-1344. 67 cases of NIP, vs 10 cases of benign nasal polyps as controls. "The total HPV infection rate of the NIP slides was 49.25%, significantly higher than that of the control group (10%)," and the infection rate of HPV types 16 and 18 was significantly higher in the group with squamous cell carcinoma.

The prevalence of human papilloma virus infection in sinonasal inverted papilloma specimens classified by histological grade. JY Kim, JK Yoon, MJ Citardi, PS Batra, HJ Roh. Am J Rhinol 2007 Nov-Dec;21(6):664-669. "The HPV DNA chip contained 22 type-specific probes that consisted of 15 high-risk subtypes and 7 low-risk subtypes. RESULTS: Histological grading was as follows: 5, grade I; 23, grade II; 22, grade III; and 7, grade IV. Seven of 57 specimens (12.3%) showed HPV DNA. All of the HPV(+) cases showed HPV DNA in early grade (grades I and II) IP lesions. No higher grade (grades III and IV) IP tumors showed HPV DNA. Among the seven HPV(+) cases, five were high-risk subtypes and two were unspecified subtypes."

Review article: relationship of human papillomavirus with papillary squamous cell carcinoma of the upper aerodigestive tract: a review. F Cobo, P Talavera, A Concha. Int J Surg Pathol 2008 Apr;16(2):127-136. "HPV detection was performed in only 22 of the 115 cases of PSCC (19%), and 11 of the 22 cases (50%) are related to this virus. The majority of cases related to HPV are produced by low-risk HPV type 6 followed by high-risk HPV type 16. Today, the association of HPV with PSCCs seems unclear because in the majority of patients tests were not performed for the detection of the HPV. This association should be clearly established to make a correct diagnosis and propose the best therapeutic strategies, such as new vaccines."

Expression of p53, p16(INK4A), pRb, p21(WAF1/CIP1), p27(KIP1), cyclin D1, Ki-67 and HPV DNA in sinonasal endophytic Schneiderian (inverted) papilloma. G Altavilla, A Staffieri, G Busatto, A Canesso, L Giacomelli, G Marioni. Acta Otolaryngol 2008 Dec 31:1-8. "HPV DNA was detected in 14/20 patients with inverted papillomas (IPs) (70%). The majority of tumours showed strong p16, p21, p27, pRb and cyclin D1 staining and little or no p53 expression. Tumours harbouring dysplasia were significantly more likely to be p53-positive and exhibit up-regulated p21 and p27, and showed altered intensity and distribution of reactive cells into and through the epithelium."

Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcome. L Alos, S Moyano, A Nadal, I Alobid, JL Blanch, E Ayala, B Lloveras, W Quint, A Cardesa, J Ordi. Cancer 2009 Apr 13;115(12):2701-2709. "HPV DNA was detected in tumor tissue of 12 of 60 (20%) patients. HPV16 was identified in 11 tumors and HPV35 in 1."

Papillary squamous cell carcinoma of the head and neck: frequent 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. 67% of sinonasal tumors were HPV-positive by ISH.

Expression of p16 in Sinonasal Undifferentiated Carcinoma (SNUC) Without Associated Human Papillomavirus (HPV). B Wadsworth, JM Bumpous, AW Martin, MR Nowacki, AB Jenson, H Farghaly. Head Neck Pathol 2011 Jul 30 [Epub ahead of print]. HPV types 6, 11, 16 or 18 were not detected in 5 cases of sinonasal undifferentiated carcinoma or in 5 poorly differentiated squamous cell carcinomas.

See also:

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 non-causal associations.

The Lie That p53 Mutations Are the Mechanism Behind Lung Cancer - this is because p53 mutations happen after maligancy has occurred, and the point is relevant to other cancers as well.

cast 08-05-11