Prevalence and Distribution of High-Risk Human Papillomavirus Genotypes in Invasive Carcinoma of the Uterine Cervix in Uruguay. An update on clinical outcome

Main Article Content

Nora Berois Fernanda Nozar Diego Greif Agustina Franciulli Enrique Barrios Eduardo Osinaga


Although the causal role of HPV in cervical cancer CC is accepted, controversial reports have been published about the prognostic significance of different genotypes. Our aim was to evaluate the HPV-status and its relationship with clinical-pathological variables and clinical outcome in invasive cervical cancer of Uruguayan women. Main prevalent genotypes were HPV16 (63.6%), HPV18 and HPV45 (8.3% each genotype), while other genotypes (HPV31, 33, 35, 39, 51, 52, 58, 66, 73 and one undetermined genotype) account for 12.4%, and in 8.3% HPV DNA could not be detected. With a mean follow-up of ten years, we found a significant correlation of overall survival with FIGO staging and lymph node metastasis. Relating to HPV, three prognostic groups were observed. The better clinical outcome was related to genotypes other than HPV16/18/45, while HPV16/18 genotypes belong to an intermediate risk group and the worse prognosis was related to HPV negative and HPV45. HPV independent tumors have been suggested as a different entity compared with virally driven ones. Improvement in knowledge of molecular pathogenesis could impact in CC patients care. In conclusion, worse prognosis was related to HPV negative and HPV45 related tumors. More research is warranted for better understanding molecular basis of virally driven or independent cervical cancer oncogenesis.

Article Details

How to Cite
BEROIS, Nora et al. Prevalence and Distribution of High-Risk Human Papillomavirus Genotypes in Invasive Carcinoma of the Uterine Cervix in Uruguay. An update on clinical outcome. Medical Research Archives, [S.l.], v. 5, n. 6, june 2017. ISSN 2375-1924. Available at: <>. Date accessed: 30 nov. 2023.
Human Papillomavirus; cervical cancer; prognosis
Research Articles


Angioli R, Lopez S, Aloisi A, Terranova C, De Cicco C, Scaletta G, Capriglione S, Miranda A, Luvero D, Ricciardi R, Montera R, Plotti F. Ten years of HPV vaccines: State of art and controversies.Crit Rev Oncol Hematol. 2016; 102:65-72. doi: 10.1016/j.critrevonc.2016.03.020.

Baiocchi G, de Brot L, Faloppa CC, Mantoan H, Duque MR, Badiglian-Filho L, da Costa AA, Kumagai LY.Is parametrectomy always necessary in early-stage cervical cancer. Gynecol Oncol. 2017; doi: 10.1016/j.ygyno.2017.03.514.

Baalbergen A, Smedts F, Ewing P, Snijders PJ, Meijer CJ, Helmerhorst TJ.HPV-type has no impact on survival of patients with adenocarcinoma of the uterine cervix. Gynecol Oncol. 2013;128(3):530-4. doi: 10.1016/j.ygyno.2012.12.013.

Barrios E, Garau M, Alonso R, Musetti C. IV Atlas de Incidencia del Cáncer en Uruguay: 2007-2011. Comisión Honoraria de Lucha Contra el Cáncer. Registro Nacional de Cáncer. 2014a; ISBN 978-9974-8157-7-3, Montevideo, Uruguay. (

Barrios E, Musetti C, et al. V Atlas de mortalidad por cáncer en el Uruguay. Periodo 2009-2013. COMISION HONORARIA DE LUCHA CONTRA EL CANCER REGISTRO NACIONAL DE CANCER – 2014b (

Berek JS, Hacker NF. Gynecologic oncology. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

Berois N, De Cremoux P, Mazal D, Sica A, Cedeira M, Caserta B, Barrios E, Osinaga E, Sastre-Garau X. Prevalence and distribution of high-risk human papillomavirus genotypes in invasive carcinoma of the uterine cervix in Uruguay. Int J Gynecol Cancer. 2013; 23(3):527-32. doi: 10.1097/IGC.0b013e318285e753.

Bosch FX, Lorincz A, Muñoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer.J Clin Pathol. 2002; 55(4):244-65.

Bradbury M, Founta C, Taylor W, Kucukmetin A, Naik R, Ang C. Pathological Risk Factors and Outcomes in Women With Stage IB2 Cervical Cancer Treated With Primary Radical Surgery Versus Chemoradiotherapy. Int J Gynecol Cancer. 2015; 25(8):1476-83. doi: 10.1097/IGC.0000000000000513.

Bucchi D, Stracci F, Buonora N, Masanotti G. Human papillomavirus and gastrointestinal cancer: A review. World J Gastroenterol. 2016; 22(33):7415-30. doi: 10.3748/wjg.v22.i33.7415.

Cuschieri K, Brewster DH, Graham C, Nicoll S, Williams AR, Murray GI, Millan D, Johannessen I, Hardie A, Cubie HA. Influence of HPV type on prognosis in patients diagnosed with invasive cervical cancer. Int J Cancer. 2014; 135(11):2721-6. doi: 10.1002/ijc.28902.

Dabić MM, Nola M, Tomicić I, Dotlić S, Petrovecki M, Jukić S. Adenocarcinoma of the uterine cervix: prognostic significance of clinicopathologic parameters, flow cytometry analysis and HPV infection. Acta Obstet Gynecol Scand. 2008; 87(3):366-72. doi: 10.1080/00016340801936560.

Dahlgren L, Erlandsson F, Lindquist D, Silfverswärd C, Hellström AC, Dalianis T. Differences in human papillomavirus type may influence clinical outcome in early stage cervical cancer. Anticancer Res. 2006; 26(2A):829-32.

de Cremoux P, de la Rochefordière A, Savignoni A, Kirova Y, Alran S, Fourchotte V, Plancher C, Thioux M, Salmon RJ, Cottu P, Mignot L, Sastre-Garau X. Different outcome of invasive cervical cancer associated with high-risk versus intermediate-risk HPV genotype. Int J Cancer. 2009; 124(4):778-82. doi: 10.1002/ijc.24075.

de Vos van Steenwijk PJ, Heusinkveld M, Ramwadhdoebe TH, Löwik MJ, van der Hulst JM, Goedemans R, Piersma SJ, Kenter GG, van der Burg SH. An unexpectedly large polyclonal repertoire of HPV-specific T cells is poised for action in patients with cervical cancer. Cancer Res. 2010; 70(7):2707-17. doi: 10.1158/0008-5472.CAN-09-4299.

Ferdousi J, Nagai Y, Asato T, Hirakawa M, Inamine M, Kudaka W, Kariya KI, Aoki Y.Impact of human papillomavirus genotype on response to treatment and survival in patients receiving radiotherapy for squamous cell carcinoma of the cervix.Exp Ther Med. 2010;1(3):525-530.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5):E359-86. doi: 10.1002/ijc.29210.

FIGO Committee on Gynecologic Oncology. FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. Int J Gynaecol Obstet. 2014; 125(2):97-8. doi: 10.1016/j.ijgo.2014.02.003.

Gadducci A, Barsotti C, Laliscia C, Cosio S, Fanucchi A, Tana R, Fabrini MG. Dose-dense Paclitaxel- and Carboplatin-based NeoadjuvantChemotherapy Followed by Surgery or Concurrent Chemo-radiotherapy in Cervical Cancer: a Preliminary Analysis. Anticancer Res. 2017; 37:1249-55.

GLOBOCAN2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. International Agency for Research on Cancer, World Health Organization. Available: pages/fact_sheets_cancer.aspx. Accessed. 3 March 2017.
Huang LW, Chao SL, Hwang JL. Human papillomavirus-31-related types predict better survival in cervical carcinoma. Cancer. 2004;100(2):327-34.

Jiamset I, Hanprasertpong J. Risk Factors for Parametrial Involvement in Early-Stage Cervical Cancer and Identification of Patients Suitable for Less Radical Surgery. Oncol Res Treat. 2016; 39(7-8):432-8. doi: 10.1159/000447335.

Kang WD, Kim CH, Cho MK, Kim JW, Cho HY, Kim YH, Choi HS, Kim SM. HPV-18 is a poor prognostic factor, unlike the HPV viral load, in patients with stage IB-IIA cervical cancer undergoing radical hysterectomy. Gynecol Oncol. 2011; 121(3):546-50. doi: 10.1016/j.ygyno.2011.01.015.

Lai CH, Chang CJ, Huang HJ, Hsueh S, Chao A, Yang JE, Lin CT, Huang SL, Hong JH, Chou HH, Wu TI, Huang KG, Wang CC, Chang TC. Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery. J Clin Oncol. 2007; 25(24):3628-34.

Lai CH, Chou HH, Chang CJ, Wang CC, Hsueh S, Huang YT, Chen YR, Chang HP, Chang SC, Lin CT, Chao A, Qiu JT, Huang KG, Chen TC, Jao MS, Chen MY, Liou JD, Huang CC, Chang TC, Patsner B. Clinical implications of human papillomavirus genotype in cervical adeno-adenosquamous carcinoma. Eur J Cancer. 2013; 49(3):633-41. doi: 10.1016/j.ejca.2012.09.008.

Landoni F, Colombo A, Milani R, Placa F, Zanagnolo V, Mangioni C. Randomized study between radical surgery and radiotherapy for the treatment of stage IB-IIA cervical cancer: 20-year update. J Gynecol Oncol. 2017; 28:e34.

Lau YM, Cheung TH, Yeo W, Mo F, Yu MY, Lee KM, Ho WC, Yeung AC, Law PT, Chan PK. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment. PLoS One. 2015; 10(4):e0122557. doi: 10.1371/journal.pone.0122557.

Liu H, Li J, Zhou Y, Hu Q, Zeng Y, Mohammadreza MM. Human papillomavirus as a favorable prognostic factor in a subset of head and neck squamous cell carcinomas: A meta-analysis. J Med Virol. 2017; 89(4):710-725. doi: 10.1002/jmv.24670.

Liu J, Westin SN. Rational selection of biomarker driven therapies for gynecologic cancers: The more we know, the more we know we don't know. Gynecol Oncol. 2016; 141:65-71. doi: 10.1016/j.ygyno.2016.01.003.

Lombard I, Vincent-Salomon A, Validire P, Zafrani B, de la Rochefordière A, Clough K, Favre M, Pouillart P, Sastre-Garau X. Human papillomavirus genotype as a major determinant of the course of cervical cancer. J Clin Oncol. 1998; 16(8):2613-9.

Mabuchi S, Okazawa M, Matsuo K, Kawano M, Suzuki O, Miyatake T, Enomoto T, Kamiura S, Ogawa K, Kimura T. Impact of histologicalsubtype on survival of patients with surgically-treated stage IA2-IIB cervical cancer: adenocarcinoma versus squamous cell carcinoma. Gynecol Oncol. 2012; 127(1):114-20. doi: 10.1016/j.ygyno.2012.06.021

Mai S, Welzel G, Ottstadt M, Lohr F, Severa S, Prigge ES, Wentzensen N, Trunk MJ, Wenz F, von Knebel-Doeberitz M, Reuschenbach M. Prognostic Relevance of HPV Infection and p16 Overexpression in Squamous Cell Anal Cancer. Int J Radiat Oncol Biol Phys. 2015; 93(4):819-27. doi: 10.1016/j.ijrobp.2015.08.004.

Mao S, Dong J, Li S, Wang Y, Wu P. Prognostic significance of number of nodes removed in patients with node-negative early cervical cancer. J Obstet Gynaecol Res. 2016; 42(10):1317-1325. doi: 10.1111/jog.13058.

Meng XY, Liao Y, Liu XP, Li S, Shi MJ, Zeng XT. Concurrent cisplatin-based chemoradiotherapy versus exclusive radiotherapy in high-risk cervical cancer: a meta-analysis. Onco Targets Ther. 2016; 9:1875-88. doi: 10.2147/OTT.S97436.

Niu G, Wang D, Pei Y, Sun L. Systematic identification of key genes and pathways in the development of invasive cervical cancer. Gene. 2017 (Mar 21). doi: 10.1016/j.gene.2017.03.018.

Okuma K, Yamashita H, Yokoyama T, Nakagawa K, Kawana K. Undetected human papillomavirus DNA and uterine cervical carcinoma: Association with cancer recurrence. Strahlenther Onkol. 2016;192(1):55-62.

Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet. 2009; 105(2):107-8. doi: 10.1016/j.ijgo.2009.02.009.

Perri F, Pacelli R, Della Vittoria Scarpati G, Cella L, Giuliano M, Caponigro F, Pepe S. Radioresistance in head and neck squamous cell carcinoma: Biological bases and therapeutic implications. Head Neck. 2015; 37(5):763-70. doi: 10.1002/hed.23837.

Pilch H, Günzel S, Schäffer U, Tanner B, Brockerhoff P, Maeurer M, Höckel M, Hommel G, Knapstein PG. The presence of HPV DNA in cervical cancer: correlation with clinico-pathologic parameters and prognostic significance: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University. Int J Gynecol Cancer. 2001; 11(1):39-48.

Riou G, Favre M, Jeannel D, Bourhis J, Le Doussal V, Orth G. Association between poor prognosis in early-stage invasive cervical carcinomas and non-detection of HPV DNA. Lancet. 1990; 335(8699):1171-4.

Rodríguez-Carunchio L, Soveral I, Steenbergen RD, Torné A, Martinez S, Fusté P, Pahisa J, Marimon L, Ordi J, del Pino M. HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis. BJOG. 2015; 122(1):119-27. doi: 10.1111/1471-0528.13071.

Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007; 370(9590):890-907.

Schwartz SM, Daling JR, Shera KA, Madeleine MM, McKnight B, Galloway DA, Porter PL, McDougall JK. Human papillomavirus and prognosis of invasive cervical cancer: a population-based study. J Clin Oncol. 2001; 19(7):1906-15.

Shah W, Hongwei C, Jin Z, Lifang D, Jun Y, Yili W. The prevalence of human papillomavirus type 58 in Chinese patients with cervical carcinoma and its influence on survival. Clin Oncol (R Coll Radiol). 2009; 21(10):768-74. doi: 10.1016/j.clon.2009.09.003.

Stevanović S, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, Restifo NP, Rosenberg SA, Hinrichs CS. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015; 33(14):1543-50. doi: 10.1200/JCO.2014.58.9093.

Tong SY, Lee YS, Park JS, Namkoong SE. Human papillomavirus genotype as a prognostic factor in carcinoma of the uterine cervix. Int J Gynecol Cancer. 2007; 17(6):1307-13

Valenciano A, Henríquez-Hernández LA, Lloret M, Pinar B, Lara PC. New biological markers in the decision of treatment of head and neck cancer patients. Clin Transl Oncol. 2014; 16(10):849-58. doi: 10.1007/s12094-014-1193-7.

Wakeham K, Kavanagh K, Cuschieri K, Millan D, Pollock KG, Bell S, Burton K, Reed NS, Graham SV. HPV status and favourable outcome in vulvar squamous cancer. Int J Cancer. 2017; 140(5):1134-1146. doi: 10.1002/ijc.30523.

Wang CC, Lai CH, Huang HJ, Chao A, Chang CJ, Chang TC, Chou HH, Hong JH. Clinical effect of human papillomavirus genotypes in patients with cervical cancer undergoing primary radiotherapy. Int J Radiat Oncol Biol Phys. 2010; 78(4):1111-20. doi: 10.1016/j.ijrobp.2009.09.021.

Willows K, Lennox G, Covens A. Fertility-sparing management in cervical cancer: balancing oncologic outcomes with reproductive success. Gynecol Oncol Res Pract. 2016; 3:9. eCollection 2016.

Wood O, Woo J, Seumois G, Savelyeva N, McCann KJ, Singh D, Jones T, Peel L, Breen MS, Ward M, Garrido Martin E, Sanchez-Elsner T, Thomas G, Vijayanand P, Woelk CH, King E, Ottensmeier C; SPARC Consortium. Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors. Oncotarget. 2016; 7(35):56781-56797. doi: 10.18632/oncotarget.10788.

Yang SH, Kong SK, Lee SH, Lim SY, Park CY. Human papillomavirus 18 as a poor prognostic factor in stage I-IIA cervical cancer following primary surgical treatment. Obstet Gynecol Sci. 2014; 57(6):492-500. doi: 10.5468/ogs.2014.57.6.492.

Zhang H, Zhang S. The expression of Foxp3 and TLR4 in cervical cancer: association with immune escape and clinical pathology. Arch Gynecol Obstet. 2017; 295(3):705-712. doi: 10.1007/s00404-016-4277-5.

Zou J, Cao Z, Zhang J, Chen T, Yang S, Huang Y, Hong D, Li Y, Chen X, Wang X, Cheng X, Lu W, Xie X. Variants in human papillomavirus receptor and associated genes are associated with type-specific HPV infection and lesion progression of the cervix. Oncotarget. 2016; 7(26):40135-40147. doi: 10.18632/oncotarget.9510.

Zhou J, Wu SG, Sun JY, Li FY, Lin HX, Chen QH, He ZY. Comparison of clinical outcomes of squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma of the uterine cervix after definitive radiotherapy: a population-based analysis. J Cancer Res Clin Oncol. 2017; 143:115-122. doi: 10.1007/s00432-016-2246-9.

Zumsteg ZS, Cook-Wiens G, Yoshida E, Shiao SL, Lee NY, Mita A, Jeon C, Goodman MT, Ho AS. Incidence of Oropharyngeal Cancer Among Elderly Patients in the United States. JAMA Oncol. 2016; 2(12):1617-1623. doi: 10.1001/jamaoncol.2016.1804.