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Human Papilloma Virus and Cancers
HUMAN PAPILLOMA VIRUS AND CANCERS
By Sameera Mohotti (BSc, MSc, MD(MA))
In recent years, it has become clear that certain types of human cancers have a viral component to their etiology. Cancers due to Human Papilloma Virus (HPV) are most common among these. This has been a study of intense research for number of years. Specific types of HPV genotypes were found to be the causative agents of some common cancers, most notable invasive cervical carcinoma. Apart from this anogenital cancer, HPV’s are also causally associated with other anogenital cancers such as cancers of vulva, vagina, penis and anus. HPV is also responsible for approximately 20-30% of head and neck cancers [1].
Association OF HPV with Cervical cancer
The link between HPV and cervical cancer is now established beyond doubts. Many epidemiological [2], [3] and molecular evidences [4] suggest the causal association of HPV’s with cervical cancer. It has been estimated that about 500,000 women acquire cervical cancers every year and 75% of this are from developing countries. In United States about 13000 cervical cancer cases are diagnosed every year and about 7000 deaths annually from prevalent disease [5].
Evidence suggests that the great majority of all grades of cervical intraepithelial neoplasia can be attributed to cancer-associated types of HPV infections [3]. It has been estimated that only about 10% of the HPV patients would develop cervical dysplasia and of these only few people would develop cervical cancer. Studies conducted on HPV DNA in a variety of genital lesions suggested that HPV types 16 and 18 are most closely associated with risk of genital cancers [4] and some of HPV types are considered to be more prevalent among cervical cancer patients in a specific geographical areas; HPV 45 in Western African [6].
The development of cervical cancer is associated with factors other than just high risk HPV infection. Factors like impaired cell mediated immunity, long term use of contraceptives and smoking also increase the risk of gaining and the persistence of HPV types which in turn may lead to cervical cancers [7],[8].
Association of HPV with other anogenital cancers
Strong links between HPV and anogenital cancers such as penile, anal, vulvar cancers have been demonstrated by many studies. These cancers are formed from lesions develop in the vagina, vulva, penis and anus as the result of sexual contact [9]. But the exact role of HPV in the natural history of anal squamous intraepithelial lesions is still unknown [10].
Studies indicate that about 1% of sexually active adults in the United States show visible genital wart and about 15 % have sub clinical infection. The most commonly detected HPV types were found to be HPV 16 and 18 [11]. But, HPV types 56, 59-64 and 71 also have been isolated in vulvar intraepithelial neoplasia [12] .
Association of HPV with head and neck cancer
The term head and neck cancer refer to the cancers in the oral cavity, lip, nose, para nasal sinuses, naso-pharynx, oro-parynx, larynx, oesophagus, salivary glands, soft tissues of the neck and ear. Oral cancer is the sixth most prevalent cancer worldwide and about 620,000 patients are diagnosed with cancer of oral cavity every year [13]. Many studies have found evidence suggestive of a role for human papilloma virus in head and neck cancer [14],[15]. Though the exact mode of transmission of HPV infection in the head and neck region has not been determined, it’s association with sexual behavior and perinatal transmission have been demonstrated [16].
During the pathogenesis of HPV, it enters to the host through the mucosal epithelial layer surface. Oral mucosa resembles the mucosa of the genital region in their histological structure. As the correlation between HPV and cervical cancer are well established, the resemblance of the mucosal histology led to the suggestion that HPV could play a role in the development of benign and malignant lesions of the oral mucosa [17].
After the first report of papilloma virus in tongue carcinoma[14], many studies have shown the presence of HPV DNA in oral cavity [15] and head and neck cancer [13]. The most prevalent HPV types in these were found to be HPV 16 and 18. Further epidemiologic and molecular investigation should be carried out to establish a precise relationship between HPV and head and neck cancer.
HPV INDUCED CANCER DETECTION
Detective measures to date have centered on screening programs for HPV induced cancers. The most common and the traditional way of screening for cervical cancer and cervical dysplasia are to conduct a pap smear test. This has significantly reduced the incidence of cervical cancers in recent years. If the result is turned out to be positive, then the colposcopy would be carried. Since cervical cancer and anal cancer resembles in their biological features, it has been observed that screening for anal high grade squamous intraepithelial lesions with anal pap smear allows detecting individuals at risk of developing anal cancers. To obtain a confirmatory result, an anoscopic examination should be performed [18, 19].
Detection of earlier stage of head and neck cancers as well as premalignant lesions can be done by regular physical examinations by the doctor. Any abnormalities should be further evaluated. An endoscopy is performed on the samples obtained from throat, larynx, and upper esophagus. Computed tomographic (CT) scans, magnetic resonances imaging (MRI) scans or ultrasounds could be performed to identify the size and extent to which the cancer has spread from its site of origin [20].
No standard screening tests are followed for vulvar cancers. In vulvar cancer lymph node pathologic status is the most important predictive factor. A study conducted by De Ceccoc et al indicated that Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance are easy and reliable methods for the detection of sentinel node in early vulvar cancer [21]. Coloscopy can also be used to detect abnormalities on vulvar epethilia [19].
The above mentioned tests cannot be used to detect the presence or absence of the virus which would eventually cause a cancer. A test based on the hybrid capture technologies is now available to detect 13 cancer causing kinds of HPV. This technology is based on the principle of signal amplification of a hybrid species produced by RNA probes fixed with HPV DNA [22]. Polymerase chain reaction is one of the most sensitive tests for HPV DNA detection [23]. But Zhao M. et al suggest that there could be limitations in this method when applying to a broad population [24]. Studies indicate that HPV DNA testing is one of the most effective tests which could be used for the prevention of cervical cancer [25].
In a study conducted by Reid et al, to compare the efficacy of cervical cytology, cervicography and/or DNA hybridization for cervical cancer screening, showed that none of the tests succeeded in identifying all the abnormalities [26].
REFERENCES
1. I. Benjamin Paz, N.C., Tamara Odom-Maryon, Yuan Xie, Sharon P. Wilczynski,, Human papillomavirus (HPV) in head and neck cancer. Cancer, 1997. 79(3): p. 595-604.
2. Koutsky, L.A., et al., A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med, 1992. 327(18): p. 1272-8.
3. Schiffman, M.H., et al., Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst, 1993. 85(12): p. 958-64.
4. JC Macnab, S.W., JW Cordiner, and JB Clements, Human papillomavirus in clinically and histologically normal tissue of patients with genital cancer. The New England Journal of Medicine, 1986. 315(17): p. 1052-1058.
5. Parkin, D.M., P. Pisani, and J. Ferlay, Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer, 1999. 80(6): p. 827-41.
6. Bosch, F.X., et al., Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst, 1995. 87(11): p. 796-802.
7. Calore, E.E., S.M. Pereira, and M.J. Cavaliere, Progression of cervical lesions in HIV-seropositive women: a cytological study. Diagn Cytopathol, 2001. 24(2): p. 117-9.
8. Brisson, J., et al., Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions. Am J Epidemiol, 1994. 140(8): p. 700-10.
9. Jung, W.W., et al., Strategies against human papillomavirus infection and cervical cancer. J Microbiol, 2004. 42(4): p. 255-66.
10. Palefsky, J.M., et al., Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer. Cancer Res, 1991. 51(3): p. 1014-9.
11. Koutsky, P., Laura, Epidemiology of Genital Human Papillomavirus Infection. The American Journal of Medicine, 1997. 102(5, Supplement 1): p. 3-8.
12. Longuet, M., S. Beaudenon, and G. Orth, Two novel genital human papillomavirus (HPV) types, HPV68 and HPV70, related to the potentially oncogenic HPV39. J. Clin. Microbiol., 1996. 34(3): p. 738-744.
13. Syrjanen, S., Human papillomavirus (HPV) in head and neck cancer. J Clin Virol, 2005. 32 Suppl 1: p. S59-66.
14. de Villiers, E.M., et al., Papillomavirus DNA in human tongue carcinomas. Int J Cancer, 1985. 36(5): p. 575-8.
15. Palefsky, J.M., et al., Association between proliferative verrucous leukoplakia and infection with human papillomavirus type 16. J Oral Pathol Med, 1995. 24(5): p. 193-7.
16. Szentirmay, Z., et al., Human papillomavirus in head and neck cancer: molecular biology and clinicopathological correlations. Cancer Metastasis Rev, 2005. 24(1): p. 19-34.
17. Woods, K.V., et al., Analysis of human papillomavirus DNA in oral squamous cell carcinomas. J Oral Pathol Med, 1993. 22(3): p. 101-8.
18. Sheary B, D.L., Cervical screening and human papillomavirus. Aust Fam Physician., 2005. 34(7): p. 578-80.
19. JD., O., Genitoanal papillomavirus infection--a diagnostic and therapeutic dilemma. Semin Dermatol., 1990. 9(2): p. 141-7.
20. Antunes, J.L.F., et al., Trends and spatial distribution of oral cancer mortality in Sao Paulo, Brazil, 1980-1998. Oral Oncology, 2001. 37(4): p. 345-350.
21. C De Cicco, M.S., M Bartolomei, C Grana, M Cremonesi, M Fiorenza, A Maggioni, L Bocciolone, C Mangioni, N Colombo and G Paganelli, Sentinel node biopsy in early vulvar cancer. British Journal of Cancer, 2000. 82: p. 295-299.
22. Thomas, R.J., Early Detection of Cervical Cancer -New diagnostics identify HPV. Modern Drug Discovery, 2000. 4: p. 57-58.
23. Miller CS, Z.M., White DK., Detection of HPV DNA in oral carcinoma using polymerase chain reaction together with in situ hybridization. Oral Surg Oral Med Oral Pathol., 1994. 77(5): p. 480-6.
24. Ming Zhao, E.R., Andre Lopes Carvalho, Wayne Koch, WeiWen Jiang, David Sidransky, Joseph Califano,, Feasibility of quantitative PCR-based saliva rinse screening of HPV for head and neck cancer. International Journal of Cancer, 2005. 117(4): p. 605-610.
25. Denny, L.A., Human papillomavirus testing and screening. Best Practice & Research Clinical Obstetrics & Gynaecology, 2005. 19(4): p. 501-15.
26. Harry, T.C.S., K.M., Evaluation of the Hybrid Capture human papillomavirus deoxyribonucleic acid detection test. American Journal of Obstetrics & Gynecology, 1996. 175(3): p. 758-9.
About the Author
Sameera Mohotti (BSc, MSc, Dip in Accu)
Human Head Found In Hamburger