Top

International Journal of Clinical Oncology

Published in:

Open Access 18-05-2023 | Human Papillomavirus | Invited Review Article

Papillomaviruses and cancer: commonalities and differences in HPV carcinogenesis at different sites of the body

Author: Nagayasu Egawa

Published in: International Journal of Clinical Oncology | Issue 8/2023

Abstract

Human papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These cancers claim > 400,000 lives annually. The persistent infection of HPV and the function of viral oncogenes are the primary causes of HPV-related cancers. However, only some HPV-infected persons or infected lesions will progress to cancer, and the burden of HPV-associated cancer varies widely according to gender and the part of the body infected. The dissimilarity in infection rates at different sites can explain only a small part of the differences observed. Much responsibility likely sits with contributions of specific epithelial cells and the cellular microenvironment at infected sites to the process of malignant transformation, both of which affect the regulation of viral gene expression and the viral life cycle. By understanding the biology of these epithelial sites, better diagnosis/treatment/management of HPV-associated cancer and/or pre-cancer lesions will be provided.

Fraumeni JF Jr, Lloyd JW, Smith EM et al (1969) Cancer mortality among nuns: role of marital status in etiology of neoplastic disease in women. J Natl Cancer Inst 42:455–468PubMed

Durst M, Gissmann L, Ikenberg H et al (1983) A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A 80:3812–3815PubMedPubMedCentral

Gissmann L, Boshart M, Durst M et al (1984) Presence of human papillomavirus in genital tumors. J Invest Dermatol 83:26s–28sPubMed

Martel Cd, Plummer M, Vignat J, et al . 2017. Worldwide burden of cancer attributable to HPV by site, country and HPV type. International Journal of Cancer 141.

Vorsters A, Bosch FX, Poljak M, et al , Prevention HPV, Control B, the International Papillomavirus S (2022) HPV prevention and control - The way forward. Prev Med 156:106960

Doorbar J, Egawa N, Griffin H et al (2015) Human papillomavirus molecular biology and disease association. Rev Med Virol 25(Suppl 1):2–23PubMedPubMedCentral

Egawa N, Egawa K, Griffin H et al (2015) Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia. Viruses 7:3863–3890PubMedPubMedCentral

Van Doorslaer K (2013) Evolution of the papillomaviridae. Virology 445:11–20PubMed

Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209–249PubMed

10.

Harden ME, Munger K. 2017. Human papillomavirus molecular biology, vol 772.

11.

Munger K, Phelps WC, Bubb V et al (1989) The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 63:4417–4421PubMedPubMedCentral

12.

Magaldi TG, Almstead LL, Bellone S et al (2012) Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation. Virology 422:114–124PubMed

13.

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMed

14.

Thomas M, Banks L (1998) Inhibition of Bak-induced apoptosis by HPV-18 E6. Oncogene 17:2943–2954PubMed

15.

Scheffner M, Werness BA, Huibregtse JM et al (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129–1136PubMed

16.

Veldman T, Liu X, Yuan H et al (2003) Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. Proc Natl Acad Sci U S A 100:8211–8216PubMedPubMedCentral

17.

McMurray HR, McCance DJ (2003) Human papillomavirus type 16 E6 activates TERT gene transcription through induction of c-Myc and release of USF-mediated repression. J Virol 77:9852–9861PubMedPubMedCentral

18.

Gewin L, Myers H, Kiyono T et al (2004) Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex. Genes Dev 18:2269–2282PubMedPubMedCentral

19.

Vande Pol SB, Klingelhutz AJ (2013) Papillomavirus E6 oncoproteins. Virology 445:115–137PubMed

20.

Thomas M, Banks L (2021) The biology of papillomavirus PDZ associations: what do they offer papillomaviruses? Curr Opin Virol 51:119–126PubMed

21.

Roman A, Munger K (2013) The papillomavirus E7 proteins. Virology 445:138–168PubMed

22.

Duensing S, Munger K (2002) The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability. Cancer Res 62:7075–7082PubMed

23.

Duensing S, Munger K (2003) Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members. J Virol 77:12331–12335PubMedPubMedCentral

24.

Duensing S, Munger K (2004) Mechanisms of genomic instability in human cancer: insights from studies with human papillomavirus oncoproteins. Int J Cancer 109:157–162

25.

Incassati A, Patel D, McCance DJ. 2006. Induction of tetraploidy through loss of p53 and upregulation of Plk1 by human papillomavirus type-16 E6. Oncogene 25:pp2444–2451.

26.

Ronco LV, Karpova AY, Vidal M et al (1998) Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 12:2061–2072PubMedPubMedCentral

27.

Park JS, Kim EJ, Kwon HJ et al (2000) Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem 275:6764–6769PubMed

28.

Antonsson A, Payne E, Hengst K et al (2006) The human papillomavirus type 16 E7 protein binds human interferon regulatory factor-9 via a novel PEST domain required for transformation. J Interferon Cytokine Res 26:455–461PubMed

29.

Lou M, Huang D, Zhou Z et al (2023) DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS-STING-triggered innate immune activation. J Med Virol 95:e28310PubMed

30.

Lau L, Gray EE, Brunette RL et al (2015) DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway. Science 350:568–571PubMed

31.

Reiser J, Hurst J, Voges M et al (2011) High-risk human papillomaviruses repress constitutive kappa interferon transcription via E6 to prevent pathogen recognition receptor and antiviral-gene expression. J Virol 85:11372–11380PubMedPubMedCentral

32.

Hong S, Mehta KP, Laimins LA (2011) Suppression of STAT-1 expression by human papillomaviruses is necessary for differentiation-dependent genome amplification and plasmid maintenance. J Virol 85:9486–9494PubMedPubMedCentral

33.

Estêvão D, Costa NR, Gil da Costa RM et al (2019) Hallmarks of HPV carcinogenesis: The role of E6, E7 and E5 oncoproteins in cellular malignancy, vol 1862.

34.

Doorbar J. 2018. Host control of human papillomavirus infection and disease. Best Pract Res Clin Obstet Gynaecol 47:pp27–41.

35.

Gravitt PE, Winer RL. 2017. Natural History of HPV Infection across the Lifespan: Role of Viral Latency. Viruses 9.

36.

Sawaya GF, McConnell KJ, Kulasingam SL et al (2003) Risk of cervical cancer associated with extending the interval between cervical-cancer screenings. N Engl J Med 349:1501–1509PubMed

37.

Bosch FX, Lorincz A, Munoz N et al (2002) The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 55:244–265PubMedPubMedCentral

38.

Cox JT, Schiffman M, Solomon D, Group A-LTS (2003) Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy. Am J Obstet Gynecol 188:1406–1412

39.

Gravitt PE (2011) The known unknowns of HPV natural history. J Clin Invest 121:4593–4599PubMedPubMedCentral

40.

Castle PE, Schiffman M, Wheeler CM et al (2009) Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 113:18–25PubMedPubMedCentral

41.

Schiffman M, Castle PE, Jeronimo J et al (2007) Human papillomavirus and cervical cancer. Lancet 370:890–907PubMed

42.

Pett M, Coleman N (2007) Integration of high-risk human papillomavirus: a key event in cervical carcinogenesis? J Pathol 212:356–367PubMed

43.

Vinokurova S, Wentzensen N, Kraus I et al (2008) Type-dependent integration frequency of human papillomavirus genomes in cervical lesions. Cancer Res 68:307–313PubMed

44.

Jeon S, Allen-Hoffmann BL, Lambert PF (1995) Integration of human papillomavirus type 16 into the human genome correlates with a selective growth advantage of cells. J Virol 69:2989–2997PubMedPubMedCentral

45.

Matsukura T, Koi S, Sugase M (1989) Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers. Virology 172:63–72PubMed

46.

Ottinger M, Smith JA, Schweiger MR et al (2009) Cell-type specific transcriptional activities among different papillomavirus long control regions and their regulation by E2. Virology 395:161–171PubMed

47.

Khare S, Pater MM, Tang SC et al (1997) Effect of glucocorticoid hormones on viral gene expression, growth, and dysplastic differentiation in HPV16-immortalized ectocervical cells. Exp Cell Res 232:353–360PubMed

48.

Mittal R, Tsutsumi K, Pater A et al (1993) Human papillomavirus type 16 expression in cervical keratinocytes: role of progesterone and glucocorticoid hormones. Obstet Gynecol 81:5–12PubMed

49.

Kyo S, Inoue M, Hayasaka N, et al . 1994. Regulation of early gene expression of human papillomavirus type 16 by inflammatory cytokines. Virology 200:pp130–139.

50.

Hleyhel M, Hleyhel M, Bouvier AM, et al , Cancer Risk Group of the French Hospital Database on HIV (2014) Risk of non-AIDS-defining cancers among HIV-1-infected individuals in France between 1997 and 2009: results from a French cohort. AIDS 28:2109–2118

51.

Dugue PA, Rebolj M, Hallas J et al (2015) Risk of cervical cancer in women with autoimmune diseases, in relation with their use of immunosuppressants and screening: population-based cohort study. Int J Cancer 136:E711–E719PubMed

52.

Stelzle D, Tanaka LF, Lee KK et al (2021) Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health 9:e161–e169PubMed

53.

Humans IWGotEoCRt. (2007) Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum 90:1–636

54.

Castle PE. 2008. How does tobacco smoke contribute to cervical carcinogenesis? J Virol 82:6084–5; author reply 6085–6.

55.

Prokopczyk B, Cox JE, Hoffmann D et al (1997) Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers. J Natl Cancer Inst 89:868–873PubMed

56.

Smith JS, Green J, Berrington de Gonzalez A et al (2003) Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 361:1159–1167PubMed

57.

Smith JS, Bosetti C, Munoz N et al (2004) Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study. Int J Cancer 111:431–439PubMed

58.

Kyrgiou M, Moscicki AB (2022) Vaginal microbiome and cervical cancer. Semin Cancer Biol 86:189–198PubMed

59.

Doorbar J, Griffin H (2019) Refining our understanding of cervical neoplasia and its cellular origins. Papillomavirus Res 7:176–179PubMedPubMedCentral

60.

Leemans CR, Snijders PJF, Brakenhoff RH (2018) The molecular landscape of head and neck cancer. Nat Rev Cancer 18:269–282PubMed

61.

Sabatini ME, Chiocca S (2020) Human papillomavirus as a driver of head and neck cancers. Br J Cancer 122:306–314PubMed

62.

Ryser MD, Rositch A, Gravitt PE (2017) Modeling of US Human Papillomavirus (HPV) Seroprevalence by Age and Sexual Behavior Indicates an Increasing Trend of HPV Infection Following the Sexual Revolution. J Infect Dis 216:604–611PubMedPubMedCentral

63.

Schache AG, Powell NG, Cuschieri KS et al (2016) HPV-Related Oropharynx Cancer in the United Kingdom: An Evolution in the Understanding of Disease Etiology. Cancer Res 76:6598–6606PubMedPubMedCentral

64.

D’Souza G, Westra WH, Wang SJ et al (2017) Differences in the Prevalence of Human Papillomavirus (HPV) in Head and Neck Squamous Cell Cancers by Sex, Race, Anatomic Tumor Site, and HPV Detection Method. JAMA Oncol 3:169–177PubMedPubMedCentral

65.

Hoots BE, Palefsky JM, Pimenta JM et al (2009) Human papillomavirus type distribution in anal cancer and anal intraepithelial lesions. Int J Cancer 124:2375–2383PubMed

66.

Palefsky JM, Lee JY, Jay N, et al (2022) Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med 386:2273–2282

67.

Zhang J, Zhang Y, Zhang Z (2018) Prevalence of human papillomavirus and its prognostic value in vulvar cancer: a systematic review and meta-analysis. PLoS ONE 13:e0204162PubMedPubMedCentral

Title: Papillomaviruses and cancer: commonalities and differences in HPV carcinogenesis at different sites of the body
Author: Nagayasu Egawa
Publication date: 18-05-2023
Publisher: Springer Nature Singapore
Keywords: Human Papillomavirus
Cervical Cancer
Cervical Cancer
Published in: International Journal of Clinical Oncology / Issue 8/2023
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-023-02340-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2023

Predictive value of circulating tumor cell counts during the treatment of cancer: interactions with the blood microenvironment

Characteristics of anal canal squamous cell carcinoma as an HPV-associated cancer in Japan

Definitive S-1/mitomycin-C chemoradiotherapy for stage II/III anal canal squamous cell carcinoma: a phase I/II dose-finding and single-arm confirmatory study (JCOG0903)

Potential efficacy of local therapy for progressive lesions after nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck

Etiology, diagnosis, treatment, and prevention of human papilloma virus-associated oropharyngeal squamous cell carcinoma

The prognostic significance of the clinical T stage and Grade Group in patients with locally advanced prostate cancer treated via high-dose-rate brachytherapy and external beam radiation

Keynote webinar | Spotlight on antibody–drug conjugates in cancer