Anal Invasive Squamous Cell Cancer and Human Papillomavirus Distribution in HIV-Infected and Non-HIV-Infected Individuals

Laila Darwich^1,2, Sebastián Videla^1,3*, Mari-Paz Cañadas^1,4, Josep Coll^1,5, Boris Revollo¹, Marta Piñol¹, Francesc García-Cuyás¹, Eva Castella¹, Bonaventura Clotet^1,5,6,7, Guillem Sirera^1,5

¹Lluita Contra La SIDA Foundation, University Hospital Germans Trias i Pujol, Badalona, Spain.
²Departament de Sanitat i d’Anatomia Animals, Faculty of Veterinary, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain.
³Department of Experimental and Health Sciences, Faculty of Health and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
⁴General-Labco, Barcelona, Spain.
⁵HIV Clinical Unit, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain.
⁶Retrovirology Laboratory IrsiCaixa Foundation, University Hospital Germans Trias i Pujol, Badalona, Spain.
⁷Universitat de Vic, Vic, Spain.

DOI: 10.4236/ijcm.2014.519148                

Abstract

Invasive-squamous-cell-cancer (ISCC) of the anal canal is an uncommon disease. Human papillomavirus (HPV) is the etiological agent of most of types of ISCC. The incidence of ISCC has been increasing in HIV-infected individuals, even after the introduction of highly active antiretroviral therapy. The aim of this study was to analyze biopsy specimens from patients diagnosed with ISCC at a tertiary hospital from 1983 to 2012 in order to detect HPV-DNA. Methods: Formaldehyde-fixed, paraffin-embedded specimens from patients with ISCC underwent HPV-DNA genotyping using multiplex PCR assay. Results: A total of 31 cases were collected; 10 were HIV-infected (9 men, 1 woman) and 21 non-HIV-infected (11 men, 10 women). HPV infection was detected in 87.5% (7/8) of the HIV-infected patients (DNA from 2 biopsies was degraded) and 76.2% (16/21) of non-HIV-infected individuals. Multiple-type infections were only found in 28.6% (2/7) of the HIV-infected patients (no multiple-type infections in non-HIV-infected individuals). The most prevalent type was HPV-16: 50% (4/8) in the HIV-infected group (57% [4/7] of the HPV-positive samples) and 66.7% (14/21) in the non-HIV-infected group (87.5% (14/16) of the HPV-positive samples). Remarkably, 37.5% (3/8) of the HIV-infected group had high-risk HPV types not included in the vaccines (HPV-33, 51, 52, and 66) compared with 4.8% in the non-HIV-infected group (1/21, HPV-52). All cases of anal ISCC in HIV-infected patients were recorded in the highly active antiretroviral therapy era. Conclusion: HIV-infected patients presented anal ISCC with a higher proportion of high-risk HPV types not covered by the conventional vaccines than non-HIV-infected individuals.

Keywords

Human Papillomavirus, Anal Invasive Squamous Cell Cancer, HIV Infection

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Ouhoummane, N., Steben, M., Coutlée, F., Vuong, T., Forest, P., Rodier, C., Louchini, R., Duarte, E. and Brassard, P. (2013) Squamous Anal Cancer: Patient Characteristics and HPV Type Distribution. Cancer Epidemiology, 37, 807-812. http://dx.doi.org/10.1016/j.canep.2013.09.015
[2]	Joseph, D.A., Miller, J.W., Wu, X., Chen, V.W., Morris, C.R., Goodman, M.T., Villalon-Gomez, J.M., Williams, M.A. and Cress, R.D. (2008) Understanding the Burden of Human Papillomavirus Associated Anal Cancers in the US. Cancer, 113, 2892-2900. http://dx.doi.org/10.1002/cncr.23744
[3]	Jin, F., Stein, A.N., Conway, E.L., Regan, D.G., Law, M., Brotherton, J.M., Hocking, J. and Grulich, A.E. (2011) Trends in Anal Cancer in Australia, 1982-2005. Vaccine, 29, 2322-2327. http://dx.doi.org/10.1016/j.vaccine.2011.01.015
[4]	Nielsen, A., Munk, C. and Kjaer, S.K. (2012) Trends in Incidence of Anal Cancer and High-Grade Anal Intraepithelial Neoplasia in Denmark, 1978-2008. International Journal of Cancer, 130, 1168-1173. http://dx.doi.org/10.1002/ijc.26115
[5]	Palefsky, J.M., Holly, E.A., Ralston, M.L., Arthur, S.P., Jay, N., Berry, J.M., Da Costa, M.M., Botts, R. and Darragh, T.M. (1998) Anal Squamous Intraepithelial Lesions in HIV-Positive and HIV-Negative Homosexual and Bisexual Men: Prevalence and Risk Factors. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 17, 320-326. http://dx.doi.org/10.1097/00042560-199804010-00005
[6]	Piketty, C., Darragh, T.M., Da Costa, M., Bruneval, P., Heard, I., Kazatchkine, M.D. and Palefsky, J.M. (2003) High Prevalence of Anal Human Papillomavirus Infection and Anal Cancer Precursors among HIV Infected Persons in the Absence of Anal Intercourse. Annals of Internal Medicine, 138, 453-459. http://dx.doi.org/10.7326/0003-4819-138-6-200303180-00008
[7]	Frisch, M., Biggar, R.J. and Goedert, J.J. (2000) Human Papillomavirus-Associated Cancers in Patients with Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome. Journal of the National Cancer Institute, 92, 1500-1510. http://dx.doi.org/10.1093/jnci/92.18.1500
[8]	Ahmed, S. and Eng, C. (2014) Optimal Treatment Strategies for Anal Cancer. Current Treatment Options in Oncology, 15, 443-455. http://dx.doi.org/10.1007/s11864-014-0298-0
[9]	Berry, J.M., Jay, N., Cranston, R.D., Darragh, T.M., Holly, E.A., Welton, M.L. and Palefsky, J.M. (2014) Progression of Anal High-Grade Squamous Intraepithelial Lesions to Invasive Anal Cancer among HIV-Infected Men Who Have Sex with Men. International Journal of Cancer, 134, 1147-1155. http://dx.doi.org/10.1002/ijc.28431
[10]	van der Loeff, M.F.S., Mooij, S.H., Richel, O., de Vries, H.J. and Prins, J.M. (2014) HPV and Anal Cancer in HIV-Infected Individuals: A Review. Current HIV/AIDS Reports, 11, 250-262. http://dx.doi.org/10.1007/s11904-014-0224-x
[11]	Glynne-Jones, R., Nilsson, P.J., Aschele, C., Goh, V., Peiffert, D., Cervantes, A. and Arnold, D. (2014) Anal Cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Radiotherapy and Oncology, 111, 330-339. http://dx.doi.org/10.1016/j.radonc.2014.04.013
[12]	Darwich, L., Videla, S., Cañadas, M.P., Piñol, M., García-Cuyàs, F., Vela, S., Molina-López, R.A., Coll, J., Sirera, G. and Clotet, B. (2013) Distribution of Human Papillomavirus Genotypes in Anal Cytological and Histological Specimens from HIV-Infected Men Who Have Sex with Men and Men Who Have Sex with Women. Diseases of the Colon & Rectum, 56, 1043-1052. http://dx.doi.org/10.1097/DCR.0b013e31829c654f
[13]	Videla, S., Darwich, L., Cañadas, M.P., Coll, J., Piñol, M., García-Cuyás, F., Molina-Lopez, R.A., Cobarsi, P., Clotet, B. and Sirera, G. (2013) Natural History of Human Papillomavirus Infections Involving Anal, Penile, and Oral Sites among HIV-Positive Men. Sexually Transmitted Diseases, 40, 3-10. http://dx.doi.org/10.1097/OLQ.0b013e31827e87bd
[14]	Villa, L.L. (2011) HPV Prophylactic Vaccination: The First Years and What to Expect from Now. Cancer Letters, 305, 106-112. http://dx.doi.org/10.1016/j.canlet.2010.12.002
[15]	Wong, A.K., Chan, R.C., Aggarwal, N., Singh, M.K., Nichols, W.S. and Bose, S. (2010) Papillomavirus Genotypes in Anal Intraepithelial Neoplasia and Anal Carcinoma as Detected in Tissue Biopsies. Modern Pathology, 23, 144-150. http://dx.doi.org/10.1038/modpathol.2009.143
[16]	Daling, J.R., Madeleine, M.M., Johnson, L.G., Schwartz, S.M., Shera, K.A., Wurscher, M.A., Carter, J.J., Porter, P.L., Galloway, D.A. and McDougall, J.K. (2004) Human Papillomavirus, Smoking, and Sexual Practices in the Etiology of anal Cancer. Cancer, 101, 270-280. http://dx.doi.org/10.1002/cncr.20365
[17]	Abramowitz, L., Jacquard, A.C., Jaroud, F., Haesebaert, J., Siproudhis, L., Pradat, P., Aynaud, O., Leocmach, Y., Soubeyrand, B., Dachez, R., Riethmuller, D., Mougin, C., Pretet, J.L. and Denis, F. (2011) Human Papillomavirus Genotype Distribution in Anal Cancer in France: The EDiTH V Study. Interna-tional Journal of Cancer, 129, 433-439. http://dx.doi.org/10.1002/ijc.25671
[18]	Hillman, R.J., Garland, S.M., Gunathilake, M.P., Stevens, M., Kumaradevan, N., Lemech, C., Ward, R.L., Meagher, A., McHugh, L., Jin, F., Carroll, S., Goldstein, D., Grulich, A.E. and Tabrizi, S.N. (2014) Short Report; Human Papillomavirus (HPV) Genotypes in an Australian Sample of Anal Cancers. International Journal of Cancer, 135, 996-1001. http://dx.doi.org/10.1002/ijc.28730
[19]	Alemany, L., Saunier, M., Alvarado-Cabrero, I., Quirós, B., Salmeron, J., Shin, H.R., Pirog, E.C., Guimerà, N., Hernandez-Suarez, G., Felix, A., Clavero, O., Lloveras, B., Kasamatsu, E., Goodman, M.T., Hernandez, B.Y., Laco, J., Tinoco, L., Geraets, D.T., Lynch, C.F., Mandys, V., Poljak, M., Jach, R., Verge, J., Clavel, C., Ndiaye, C., Klaustermeier, J., Cubilla, A., Castellsagué, X., Bravo, I.G., Pawlita, M., Quint, W.G., Muñoz, N., Bosch, F.X. and de Sanjosé, S. (2014) HPV DNA Prevalence and Type Distribution in Anal Carcinomas Worldwide. International Journal of Cancer, Early View. http://dx.doi.org/10.1002/ijc.28963
[20]	Darwich, L., Cañadas, M.P., Sirera, G., Alameda, F., Forcada, P., Delas, J., Fernández, I., Llatjós, M., Coll, J., Clotet, B. and Videla, S. (2011) Human Papillomavirus Genotype Distribution and Human Papillomavirus 16 and Human Papillomavirus 18 Genomic Integration in Invasive and in Situ Cervical Carcinoma in Human Immunodeficiency Virus-Infected Women. International Journal of Gynecological Cancer, 21, 1486-1490. http://dx.doi.org/10.1097/IGC.0b013e31822a0195
[21]	De Vuyst, H., Clifford, G.M., Nascimento, M.C., Madeleine, M.M. and Franceschi, S. (2009) Prevalence and Type Distribution of Human Papillomavirus in Carcinoma and Intraepithelial Neoplasia of the Vulva, Vagina and Anus: A Meta-Analysis. International Journal of Cancer, 124, 1626-1636. http://dx.doi.org/10.1002/ijc.24116