Prognostic value of Dna and Mrna E6/e7 of human papillomavirus in the evolution of cervical intraepithelial neoplasia grade 2

Objective: This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL).Methods: This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months.Results: Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status (P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status (P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant.Conclusions: The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution. © the authors.This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL).Methods: This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months.Results: Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status (P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status (P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant.Conclusions: The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution9152

Diagnostic and therapeutic challenges in the management of glandular abnormalities of the cervix

Glandular abnormalities comprise less than one-quarter of the diseases affecting the uterine cervix. The acquisition of knowledge on the epidemiological and biological features of glandular lesions of the cervix has occurred more slowly compared with the progress associated with squamous cell lesions. This difference is principally due to the greater prevalence of squamous cells lesions compared with that of glandular lesions. Evidence-based management guidelines are lacking for the most severe forms of glandular abnormalities of the cervix, in particular for invasive adenocarcinomas. This review summarizes the epidemiology, natural history and diagnosis of glandular abnormalities of the cervix and the current debate on the management of cervical in situ and invasive adenocarcinomas.Glandular abnormalities comprise less than one-quarter of the diseases affecting the uterine cervix. The acquisition of knowledge on the epidemiological and biological features of glandular lesions of the cervix has occurred more slowly compared with the progress associated with squamous cell lesions. This difference is principally due to the greater prevalence of squamous cells lesions compared with that of glandular lesions. Evidence-based management guidelines are lacking for the most severe forms of glandular abnormalities of the cervix, in particular for invasive adenocarcinomas. This review summarizes the epidemiology, natural history and diagnosis of glandular abnormalities of the cervix and the current debate on the management of cervical in situ and invasive adenocarcinomas71495

Phylogenetic Classification Of Human Papillomavirus Genotypes In High-grade Cervical Intraepithelial Neoplasia In Women From A Densely Populated Brazilian Urban Region

CONTEXT AND OBJECTIVE: Differences in human papillomavirus (HPV) types may correlate with the biological potential and invasion risk of high-grade cervical intraepithelial neoplasia (CIN 2 and CIN 3). The objective of this study was to determine the relationship between different combinations of HPV types and CIN severity. DESIGN AND SETTING: Cross-sectional study, at Universidade Estadual de Campinas (Unicamp). METHODS: Cervical samples from 106 women treated due to CIN 2 (18) or CIN 3 (88) were examined for specific HPV genotypes using Roche Linear Array® (LA-HPV). The proportions of CIN 2 and CIN 3 in groups of women infected with the HPV phylogenetic groups A7 and A9 were compared. Three groups were formed: women with single infections; multiple infections; and the whole sample. RESULTS: Multiple infections were detected in 68 samples (64.7%). The most frequent high-risk genotypes detected (single/multiple) were HPV 16 (57.1%), HPV 58 (24.7%), HPV 33 (15.2%), HPV 52 (13.3%), HPV 31 (10.4%), HPV 51 (7.6%) and HPV 18 (6.6%). Women without infection with HPV species Alpha 9 were less likely to have CIN 3 than were their Alpha 9 HPV-infected counterparts. HPV 16 and/or HPV 18, with or without associations with other viral types, were more frequently found in women with CIN 3 than in those with CIN 2. CONCLUSIONS: The severity of high-grade CIN may be aggravated by the presence of HPV types included in the Alpha 9 phylogenetic classification and by infections including HPV 16 and 18, singly or in combination with other HPV genotypes.1273122127Walboomers, J.M.M., Jacobs, M.V., Manos, M.M., Bosch, F.X., Kummer, J.A., Shah, K.V., Snijders, P.J.F., Munoz, N., Human papillomavirus is a necessary cause of invasive cervical cancer worldwide (1999) Journal of Pathology, 189 (1), pp. 12-19. , DOI 10.1002/(SICI)1096-9896(199909)189:13.0.CO;2-FClifford, G.M., Smith, J.S., Aguado, T., Franceschi, S., Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: A meta-analysis (2003) British Journal of Cancer, 89 (1), pp. 101-105. , DOI 10.1038/sj.bjc.6601024Munoz, N., Bosch, F.X., De Sanjose, S., Herrero, R., Castellsague, X., Shah, K.V., Snijders, P.J.F., Meijer, C.J.L.M., Epidemiologic classification of human papillomavirus types associated with cervical cancer (2003) New England Journal of Medicine, 348 (6), pp. 518-527. , DOI 10.1056/NEJMoa021641Moscicki, A.B., Schiffman, M., Kjaer, S., Villa, L.L., Chapter 5: Updating the natural history of HPV and anogenital cancer (2006) Vaccine, 24 (SUPPL. 3), pp. S3/S42-51Baak, J.P.A., Kruse, A.-J., Robboy, S.J., Janssen, E.A.M., Van Diermen, B., Skaland, I., Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers (2006) Journal of Clinical Pathology, 59 (10), pp. 1017-1028. , DOI 10.1136/jcp.2005.027839Syrjänen, K.J., Syrjänen, S.M., (2000) Papillomavirus Infections in Human Pathology, , England: John Wiley & Sons LtdSnijders, P.J.F., Steenbergen, R.D.M., Heideman, D.A.M., Meijer, C.J.L.M., HPV-mediated cervical carcinogenesis: Concepts and clinical implications (2006) Journal of Pathology, 208 (2), pp. 152-164. , DOI 10.1002/path.1866Smith, J.S., Lindsay, L., Hoots, B., Keys, J., Franceschi, S., Winer, R., Clifford, G.M., Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update (2007) International Journal of Cancer, 121 (3), pp. 621-632. , DOI 10.1002/ijc.22527Zuna, R.E., Allen, R.A., Moore, W.E., Lu, Y., Mattu, R., Dunn, S.T., Distribution of HPV genotypes in 282 women with cervical lesions: Evidence for three categories of intraepithelial lesions based on morphology and HPV type (2007) Modern Pathology, 20 (2), pp. 167-174. , DOI 10.1038/modpathol.3800723, PII 3800723Zuna, R.E., Allen, R.A., Moore, W.E., Mattu, R., Dunn, S.T., Comparison of human papillomavirus genotypes in high-grade squamous intraepithelial lesions and invasive cervical carcinoma: Evidence or differences in biologic potential of precursor lesions (2004) Mod Pathol, 17 (11), pp. 1314-1322De Villiers, E.M., Fauquet, C., Broker, T.R., Bernard, H.U., Zur Hausen, H., Classification of papillomaviruses (2004) Virology, 324 (1), pp. 17-27Liaw, K.-L., Hildesheim, A., Burk, R.D., Gravitt, P., Wacholder, S., Manos, M.M., Scott, D.R., Schiffman, M., A prospective study of human papillomavirus (HPV) type 16 DNA detection by polymerase chain reaction and its association with acquisition and persistence of other HPV types (2001) Journal of Infectious Diseases, 183 (1), pp. 8-15. , DOI 10.1086/317638Rousseau, M.C., Pereira, J.S., Prado, J.C., Villa, L.L., Rohan, T.E., Franco, E.L., Cervical coinfection with human papillomavirus (HPV) types as a predictor of acquisition and persistence of HPV infection (2001) J Infect Dis, 184 (12), pp. 1508-1517Weissenborn, S.J., Funke, A.M., Hellmich, M., Oncogenic human papillomavirus DNA loads in human immunodeficiency virus-positive women with high-grade cervical lesions are strongly elevated (2003) J Clin Microbiol, 41 (6), pp. 2763-2767Woodman, C.B.J., Collins, S.I., Young, L.S., The natural history of cervical HPV infection: Unresolved issues (2007) Nature Reviews Cancer, 7 (1), pp. 11-22. , DOI 10.1038/nrc2050, PII NRC2050Trottier, H., Mahmud, S., Costa, M.C., Sobrinho, J.P., Duarte-Franco, E., Rohan, T.E., Ferenczy, A., Franco, E.L., Human papillomavirus infections with multiple types and risk of cervical neoplasia (2006) Cancer Epidemiology Biomarkers and Prevention, 15 (7), pp. 1274-1280. , DOI 10.1158/1055-9965.EPI-06-0129Scully, R.E., Bonfiglio, T.A., Kurman, R.J., Silverberg, S.G., Wilkinson, E.J., (1994) Histological Typing of Female Genital Tract Tumors. (International Histological Classification of Tumors), , 2nd ed. Berlin: Springer-VerlagGravitt, P.E., Peyton, C.L., Alessi, T.Q., Improved amplification of genital human papillomaviruses (2000) J Clin Microbiol, 38 (1), pp. 357-361Castle, P.E., Sadorra, M., Garcia, F., Holladay, E.B., Kornegay, J., Pilot study of a commercialized human papillomavirus (HPV) genotyping assay: Comparison of HPV risk group to cytology and histology (2006) Journal of Clinical Microbiology, 44 (11), pp. 3915-3917. , DOI 10.1128/JCM.01305-06Gargiulo, F., De Francesco, M.A., Schreiber, C., Ciravolo, G., Salinaro, F., Valloncini, B., Manca, N., Prevalence and distribution of single and multiple HPV infections in cytologically abnormal cervical samples from Italian women (2007) Virus Research, 125 (2), pp. 176-182. , DOI 10.1016/j.virusres.2006.12.017, PII S0168170206003960Giuliani, L., Coletti, A., Syrjanen, K., Favalli, C., Ciotti, M., Comparison of DNA sequencing and Roche Linear array in human papillomavirus (HPV) genotyping (2006) Anticancer Research, 26 (5 B), pp. 3939-3941Woo, Y.L., Damay, I., Stanley, M., Crawford, R., Sterling, J., The use of HPV Linear Array Assay for multiple HPV typing on archival frozen tissue and DNA specimens (2007) Journal of Virological Methods, 142 (1-2), pp. 226-230. , DOI 10.1016/j.jviromet.2007.01.029, PII S0166093407000560Coutlee, F., Rouleau, D., Petignat, P., Ghattas, G., Kornegay, J.R., Schlag, P., Boyle, S., Montaner, J., Enhanced detection and typing of human papillomavirus (HPV) DNA in anogenital samples with PGMY primers and the linear array HPV genotyping test (2006) Journal of Clinical Microbiology, 44 (6), pp. 1998-2006. , DOI 10.1128/JCM.00104-06Meijer, C.J., Snijders, P.J., Castle, P.E., Clinical utility of HPV genotyping (2006) Gynecol Oncol, 103 (1), pp. 12-17Pretet, J.-L., Jacquard, A.-C., Carcopino, X., Monnier-Benoit, S., Averous, G., Soubeyrand, B., Leocmach, Y., Riethmuller, D., Human papillomavirus genotype distribution in high grade cervical lesions (CIN 2/3) in France: EDITH study (2008) International Journal of Cancer, 122 (2), pp. 424-427. , DOI 10.1002/ijc.23093Wheeler, C.M., Hunt, W.C., Schiffman, M., Castle, P.E., Human papillomavirus genotypes and the cumulative 2-year risk of cervical precancer (2006) J Infect Dis, 194 (9), pp. 1291-1299. , Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study GroupHarper, D.M., Franco, E.L., Wheeler, C.M., Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: Follow-up from a randomised control trial (2006) Lancet, 367 (9518), pp. 1247-125

A Portrait Of Single And Multiple Hpv Type Infections In Brazilian Women Of Different Age Strata With Squamous Or Glandular Cervical Lesions

Background: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients' age and lesion pathological status.Methods: 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata.Results: 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59.Conclusions: Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18. © 2014 Resende et al.; licensee BioMed Central Ltd.141Globocan 2008. Planning and Implementing Cervical Cancer Prevention and Control Programs - A manual for managers. Alliance for Cervical Cancer Prevention 2008 http://screening.iarc.fr/manual/ACCP_screen.pdf, IARC - International Agency for Research on Cancer. World Health OrganizationMinistério da Saúde. Coordenação nacional de prevenção e vigilância do câncer. Incidência do câncer no Brasil 2012 http://www.inca.gov.br/estimativa/2014/, INCA - Instituto Nacional do CâncerZur, H.H., Papillomaviruses and cancer: from basic studies to clinical application (2002) Nat Rev Cancer, 2 (5), pp. 342-350. , 10.1038/nrc798, 12044010Schiffman, M., Castle, P.E., Human Papillomavirus: epidemiology and public health (2003) Arch Pathol Lab Med, 127 (8), pp. 930-934Chen, H.C., You, S.L., Hsieh, C.Y., Schiffman, M., Lin, C.Y., Pan, M.H., Chou, Y.C., Chen, C.J., Prevalence of genotype-specific human papillomavirus infection and cervical neoplasia in Taiwan: a community-based survey of 10,602 women (2011) Int J Cancer, 128 (5), pp. 1192-1203. , 10.1002/ijc.25685, 20853317, CBCSP-HPV Study GroupKhan, S., Jaffer, N.N., Khan, M.N., Rai, M.A., Shafiq, M., Ali, A., Pervez, S., Ali, S.H., Human papillomavirus subtype 16 is common in Pakistani women with cervical carcinoma (2007) Int J Infect Dis, 11 (4), pp. 313-317. , 10.1016/j.ijid.2006.06.007, 17291804Mirabello, L., Schiffman, M., Ghosh, A., Rodriguez, A.C., Vasiljevic, N., Wentzensen, N., Herrero, R., Lorincz, A.T., Elevated methylation of HPV16 DNA is associated with the development of high grade cervical intraepithelial neoplasia (2013) Int J Cancer, 132 (6), pp. 1412-1422. , 10.1002/ijc.27750, 3493709, 22847263Pantawala, I.Y., Bauer, H.M., Miyamoto, J., Park, I.U., Huchko, M.J., Smith-McCune, K.K., A systematic review of randomized trials assessing human papillomavirus testing in cervical cancer screening (2013) Am J Obstet Gynecol, 208 (5), pp. 343-353. , 10.1016/j.ajog.2012.11.013, 3686555, 23159693Schiffman, M., Castle, P.E., Jeronimo, J., Rodriguez, A.C., Wacholder, S., Human Papillomavirus and cervical cancer (2007) Lancet, 370 (9590), pp. 890-907. , 10.1016/S0140-6736(07)61416-0, 17826171Kjær, S.K., Frederiksen, K., Munk, C., Iftner, T., Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence (2010) J Natl Cancer Inst, 102 (19), pp. 1478-1488. , 10.1093/jnci/djq356, 2950170, 20841605Argyri, E., Papaspyridakos, S., Tsimplaki, E., Michala, L., Myriokefalitaki, E., Papassideri, I., Daskalopoulou, D., Panotopoulou, E., A cross sectional study of HPV type prevalence according to age and cytology (2013) BMC Infect Dis, 13, p. 53. , 10.1186/1471-2334-13-53, 3575232, 23363541Pista, A., de Oliveira, C.F., Cunha, M.J., Paixao, M.T., Real, O., Prevalence of human papillomavirus infection in women in Portugal: the CLEOPATRE Portugal Study (2011) Int J Gynecol Cancer, 21 (6), pp. 1150-1158. , 10.1097/IGC.0b013e31821dd3b2, 21792018Wentzensen, N., Sun, C., Ghosh, A., Kinney, W., Mirabello, L., Wacholder, S., Shaber, R., Burk, R.D., Methylation of HPV18, HPV31, and HPV45 genomes and cervical intraepithelial neoplasia grade 3 (2012) J Natl Cancer Inst, 104 (22), pp. 1738-1749. , 10.1093/jnci/djs425, 3571257, 23093560Nayar, R., Solomon, D., Second edition of The Bethesda System for reporting cervical cytology - atlas, website, and Bethesda interobserver reproducibility project (2004) CytoJournal, 1 (1), p. 4. , 10.1186/1742-6413-1-4, 526759, 15504231Scully, R.E., Bonfiglio, T.A., Kurman, R.J., Silverberg, S.G., Wilkins, E.J., Histological Typing of Female Genital Tract Tumors (1994) World Health Organization. International Histological Classification of Tumors, pp. 36-49. , Berlin: Springer-Verlag, 2Simonella, L.M., Lewis, H., Smith, M., Neal, H., Bromhead, C., Canfell, K., Type-specific oncogenic human papillomavirus infection in high grade cervical disease in New Zealand (2013) BMC Infect Dis, 13, p. 114. , 10.1186/1471-2334-13-114, 3607885, 23452957Quint, K.D., de Koning, M.N., van Doorn, L.J., Quint, W.G., Pirog, E.C., HPV genotyping and HPV16 variant analysis in glandular and squamous neoplastic lesions of the uterine cervix (2010) Gynecol Oncol, 117 (2), pp. 297-301. , 10.1016/j.ygyno.2010.02.003, 20207397Kirschner, B., Schledermann, D., Holl, K., Rosenlund, M., Raillard, A., Quint, W., Molijn, A., Junge, J., HPV-genotypes in high-grade intraepithelial cervical lesions in Danish women (2013) Acta Obstet Gynecol Scand, 92 (9), pp. 1032-1040. , 10.1111/aogs.12162, 23647074Roteli-Martins, C.M., de Carvalho, N.S., Naud, P., Teixeira, J., Borba, P., Derchain, S., Tyring, S., Dubin, G., Prevalence of human papillomavirus infection and associated risk factors in young women in Brazil, Canada, and the United States: a multicenter cross-sectional study (2011) Int J Gynecol Pathol, 30 (2), pp. 173-184Balbi, G., Napolitano, A., Giordano, F., Capuano, S., Manganaro, M.A., Di Martino, L., Fusco, D., Seguino, E., Role of the association of high-risk HPV identified by real-time PCR in cervical preneoplastic lesions (2012) Eur J Gynaecol Oncol, 33 (5), pp. 467-471Trottier, H., Mahmud, S., Costa, M.C., Sobrinho, J.P., Duarte-Franco, E., Rohan, T.E., Ferenczy, A., Franco, E.L., Human papillomavirus infections with multiple types and risk of cervical neoplasia (2006) Cancer Epidemiol Biomarkers Prev, 15 (7), pp. 1274-1280. , 10.1158/1055-9965.EPI-06-0129, 16835323Figueiredo Alves, R.R., Turchi, M.D., Santos, L.E., Guimarães, E.M., Garcia, M.M., Seixas, M.S., Villa, L.L., Alves, M.D., Prevalence, genotype profile and risk factors for multiple human papillomavirus cervical infection in unimmunized female adolescents in Goiania, Brazil: a community-based study (2013) BMC Public Health, 13 (1), p. 1041. , 10.1186/1471-2458-13-1041, 3819257, 24188572Campos, N.G., Rodriguez, A.C., Castle, P.E., Herrero, R., Hildesheim, A., Katki, H., Kim, J.J., Schiffman, M., Persistence of concurrent infections with multiple human papillomavirus types: a population-based cohort study (2011) J Infect Dis, 203, pp. 823-827. , 10.1093/infdis/jiq131, 3071138, 21257737Smith, J.S., Lindsay, L., Hoots, B., Keys, J., Franceschi, S., Winer, R., Clifford, G.M., Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update (2007) Int J Cancer, 121 (3), pp. 621-632. , 10.1002/ijc.22527, 17405118Oliveira-Silva, M., Lordello, C.X., Zardo, L.M., Bonvicino, C.R., Moreira, M.A., Human Papillomavirus in Brazilian women with and without cervical lesions (2011) Virol J, 8, p. 4. , 10.1186/1743-422X-8-4, 3024957, 21208414Fernandes, J.V., Meissner, R.V., Carvalho, M.G., Fernandes, T.A., Azevedo, P.R., Sobrinho, J.S., Prado, J.C., Villa, L.L., Prevalence of human papillomavirus in archival samples obtained from patients with cervical pre-malignant and malignant lesions from Northeast Brazil (2010) BMC Res Notes, 3 (1), p. 96. , 10.1186/1756-0500-3-96, 2857859, 20377903Van de Velde, N., Boily, M.C., Drolet, M., Franco, E.L., Mayrand, M.H., Kliewer, E.V., Coutlée, F., Brisson, M., Population-level impact of the bivalent, quadrivalent, and nonavalent human Papillomavirus Vaccines: a model-based analysis (2012) J Natl Cancer Inst, 104, pp. 1712-1723. , 10.1093/jnci/djs395, 2310432

Association between Hpv types and species groups and cervical neoplasia from a high-risk area for cervical cancer, Goiânia, Brazil

CNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOThis study was designed to evaluate the effect of single or multiple-human papillomavirus (HPV) infection and phylogenetic groups on the prevalence and severity of cervical intraepithelial neoplasia (CIN) in women undergoing colposcopy after an abnormal cervical smear. Colposcopy was performed in 198 cases and biopsy was performed in 193 patients. All specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay. The overall prevalence of HPV infection in women with an abnormal cervical smear was 86% (171 of 198). The prevalence of HPV 16 in high-grade CIN (2/3) was 52% (40 of 76), being detected in 88.8% of cases (8 of 9) of invasive carcinoma. The prevalence of HPV types 31 and 35 in high-grade CIN was 10.5% (8 of 76) and 6.6% (5 of 76), respectively. Single or multiple-type infection involving HPV 16 were significantly associated with a diagnosis of high-grade neoplasia (≥2) [odds ratio (OR) 6.49; 95% confidence interval (CI): 1.88-23.44 and OR: 3.65; 95% CI: 1.13-12.15] even after adjustment for HPV-DNA. A statistically significant association was also found between HPV 16 and the other HPV types belonging to species α 9 and a diagnosis of high-grade neoplasia (OR: 7.62; 95% CI: 1.28-51.58); however, no association was found between HPV 16 and the other HPV types belonging to species α 7. HPV 16 is the most important predictor of high-grade cervical neoplasia. Multiple-type infections are predictors of high-grade cervical neoplasia when type 16 is present. © 2011 International Society of Gynecological Pathologists.This study was designed to evaluate the effect of single or multiple-human papillomavirus (HPV) infection and phylogenetic groups on the prevalence and severity of cervical intraepithelial neoplasia (CIN) in women undergoing colposcopy after an abnormal cervical smear. Colposcopy was performed in 198 cases and biopsy was performed in 193 patients. All specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay. The overall prevalence of HPV infection in women with an abnormal cervical smear was 86% (171 of 198). The prevalence of HPV 16 in high-grade CIN (2/3) was 52% (40 of 76), being detected in 88.8% of cases (8 of 9) of invasive carcinoma. The prevalence of HPV types 31 and 35 in high-grade CIN was 10.5% (8 of 76) and 6.6% (5 of 76), respectively. Single or multiple-type infection involving HPV 16 were significantly associated with a diagnosis of high-grade neoplasia (≥2) [odds ratio (OR) 6.49; 95% confidence interval (CI): 1.88-23.44 and OR: 3.65; 95% CI: 1.13-12.15] even after adjustment for HPV-DNA. A statistically significant association was also found between HPV 16 and the other HPV types belonging to species α 9 and a diagnosis of high-grade neoplasia (OR: 7.62; 95% CI: 1.28-51.58); however, no association was found between HPV 16 and the other HPV types belonging to species α 7. HPV 16 is the most important predictor of high-grade cervical neoplasia. Multiple-type infections are predictors of high-grade cervical neoplasia when type 16 is present303288294CNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçã

Atypical Glandular Cells And Adenocarcinoma In Situ According To The Bethesda 2001 Classification: Cytohistological Correlation And Clinical Implications

Background: The objective of this study was to evaluate the correlation between the 2001 Bethesda classification of endocervical glandular abnormalities and histological diagnosis. Study design: A series of 155 women with endocervical glandular abnormalities on cervical smears were included: 91 with atypical glandular cells (AGC) not otherwise specified (NOS), 15 with AGC-favor neoplastic (FN); 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) as combined diagnosis and 14 with adenocarcinoma in situ (AIS). Results: Histological outcome of squamous neoplasias (CIN 2 or worse) and adenocarcinoma were significantly associated with AGC-FN and AIS, taking as reference AGC-NOS, and more associated with AIS than AGC-FN. Similar associations were observed for histological outcome of adenocarcinoma, but no association was observed for only squamous neoplasia. Histological outcome of CIN2 or worse was strongly associated with AGC when HSIL was also present, but no association was observed with only for adenocarcinoma histological outcome. Conclusions: AGC-NOS, AGC-FN and AIS cytological diagnosis represent a progressively increasing association with neoplastic diagnosis, due to progressively increasing association with adenocarcinoma. Histological outcome of squamous neoplasia is frequent but does not differ with these cytological interpretations. The presence of HSIL associated with AGC represents greater probability of squamous neoplasia but not adenocarcinoma. © 2007 Elsevier Ireland Ltd. All rights reserved.13917985Tam, K.F., Cheung, A.N., Liu, K.L., A retrospective review on atypical glandular cells of undetermined significance (AGUS) using the Bethesda 2001 classification (2003) Gynecol Oncol, 91 (3), pp. 603-607Scheiden, R., Wagener, C., Knolle, U., Dippel, W., Capesius, C., Atypical glandular cells in conventional cervical smears: incidence and follow-up (2004) BMC Cancer, 4, p. 37Wright Jr., T.C., Cox, J.T., Massad, L.S., Twiggs, L.B., Wilkinson, E.J., 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities (2002) JAMA, 287 (16), pp. 2120-2129. , ASCCP-Sponsored Consensus ConferenceCovell, J.L., Wilbur, D.C., Guidos, B., Lee, K.R., Chhieng, D.C., Mody, D.R., Epithelial abnormalities: glandular (2004) The Bethesda System for reporting cervical cytology: definitions, criteria and explanatory notes, pp. 123-156. , Solomon D., and Nayar R. (Eds), Springer-Verlag, New YorkCangiarella, J.F., Chhieng, D.C., Atypical glandular cells-an update (2003) Diagn Cytopathol, 29 (5), pp. 271-279Daniel, A., Barreth, D., Schepansky, A., Johnson, G., Capstick, V., Faught, W., Histologic and clinical significance of atypical glandular cells on pap smears (2005) Int J Gynaecol Obstet, 91 (3), pp. 238-242Levine, L., Lucci III, J.A., Dinh, T.V., Atypical glandular cells: new Bethesda Terminology and Management Guidelines (2003) Obstet Gynecol Surv, 58 (6), pp. 399-406Derchain, S.F., Rabelo-Santos, S.H., Sarian, L.O., Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears (2004) Gynecol Oncol, 95 (3), pp. 618-623Chhieng, D.C., Elgert, P.A., Cangiarella, J.F., Cohen, J.M., Clinical significance of atypical glandular cells of undetermined significance. A follow-up study from an academic medical center (2000) Acta Cytol, 44 (4), pp. 557-566Simsir, A., Hwang, S., Cangiarella, J., Glandular cell atypia on Papanicolaou smears: interobserver variability in the diagnosis and prediction of cell of origin (2003) Cancer, 99 (6), pp. 323-330Chhieng, D.C., Gallaspy, S., Yang, H., Roberson, J., Eltoum, I., Women with atypical glandular cells: a long-term follow-up study in a high-risk population (2004) Am J Clin Pathol, 122 (4), pp. 575-579Sharpless, K.E., Schnatz, P.F., Mandavilli, S., Greene, J.F., Sorosky, J.I., Dysplasia associated with atypical glandular cells on cervical cytology (2005) Obstet Gynecol, 105 (3), pp. 494-500. , [Erratum in: Obstet Gynecol 2005;105(6):1495]Selvaggi, S.M., Cytologic features of high-grade squamous intraepithelial lesions involving endocervical glands on ThinPrep cytology (2002) Diagn Cytopathol, 26 (3), pp. 181-185Segal, A., Frost, F.A., Miranda, A., Fletcher, C., Sterrett, G.F., Predictive value of diagnoses of endocervical glandular abnormalities in cervical smears (2003) Pathology, 35 (3), pp. 198-203Solomon D, Davey D, Kurman R, et al. 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Cytopathic Effects Of Human Papillomavirus Infection And The Severity Of Cervical Intraepithelial Neoplasia: A Frequency Study

Cytopathic effects related to the human papillomavirus (HPV) infection are more frequently found in cervical intraepithelial neoplasia (CIN) 1; however, there are indications that at least half the histological diagnoses of CIN2 and CIN3 include koilocytosis areas. The objective of this study was to evaluate the frequency of the cytological criteria suggestive of HPV infection in the cervical smears of women with a histological diagnosis of CIN. One hundred and sixty-two women with abnormal cervical smears and a diagnosis of CIN confirmed by histopathology were selected, including 46 cases of CIN 1, 42 of CIN 2 and 74 cases of CIN 3. Koilocytosis was found in 63% of the smears from women with a histopathological diagnosis of CIN 1. This sign was observed in 26.2% and 25.7% of smears of women with a diagnosis of CIN 2 and CIN 3, respectively. Cytomegaly also was frequent in cervical smears of women with histopathological diagnosis of CIN 1 (71.8%). On the other hand, spindle cells and atypical metaplasia were more frequent in women with CIN 2 and CIN 3. Atypical parakeratosis showed similar frequency in all grades of CIN diagnosis. Koilocytois and cytomegaly were inversely correlated with the diagnosis of CIN2 or CIN 3, with OR values respectively of 0.30 (95%CI 0.13-0.68) and 0.26 (95%CI 0.11-0.58). The others signs analyzed did not show any significant association. Koilocitosis and cytomegaly can provides good reassurance that a patient with atypical cervical smear have CIN 1. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.4010871875Crum, C.P., Cibas, E.S., Lee, K.R., (1997) Pathology of Early Cervical Neoplasia, pp. 47-66. , New York: Churchill Livingstone;. pMcKee, G.T., (1997) Citopatologia, pp. 51-58. , Barcelona, Spain: Times Mirror Inational Publishers LTDASnijders, P.J., Steenbergen, R.D., Heideman, D.A., Meijer, C.J., HPV-mediated cervical carcinogenesis: Concepts and clinical implications (2006) J Pathol, 208, pp. 152-164Woodman, C.B., Collins, S.I., Young, L.S., The natural history of cervical HPV infection: Unresolved issues (2007) Nat Rev Cancer, 7, pp. 11-22Zuna, R.E., Allen, R.A., Moore, W.E., Lu Ymattu, R., Dunn, S.T., Distribution of HPV genotypes in 282 women with cervical lesions: Evidence for three categories of intraepithelial lesions based on morphology and HPV type (2007) Mod Pathol, 20, pp. 167-174Durst, M., Glitz, D., Schneider, A., Zur Hausen, H., Human papillomavirus type 16 (HPV16) gene expression and DNA replication in cervical neoplasia: Analysis by in situ hybridization (1992) Virology, 189, pp. 132-140Li, W., Wang, W., Si, M., Han, L., Gao, Q., Luo, A., Li, Y., Ma, D., The physical state of HPV16 infection and its clinical significance in cancer precursor lesion and cervical carcinoma (2008) J Cancer Res Clin Oncol, 134, pp. 1355-1361Wright Jr., T.C., Massad, L.S., Dunton, C.J., Spitzer, M., Wilkinson, E.J., Solomon, D., American Society for colposcopy and cervical pathology-sponsored consensus conference. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests (2006) Am J Obstet Gynecol, 197, pp. 346-355Schneider, A., Meinhardt, G., De Villiers, E.M., Gissmann, L., Sensitivy of the cytologic diagnosis of cervical condyloma in comparison with HPV-DNA hybridization stududies (1987) Diagn Cytopathol, 3, pp. 250-255Zuna, R.E., Wang, S.S., Schiffman, M., Solomon, D., Comparasion of human papillomavirus distribuition in cytologic subgroups of low-grade squamous intraepithelial lesion (2006) Cancer, 108, pp. 288-297Woodhouse, S.L., Stastny, J.F., Styer, P.E., Kennedy, M., Praestgaard, A.H., Davey, D.D., Interobserver variability in subclassification of squamous intraepithelial lesions: Results of the college of American pathologists interlaboratory comparison program in cervicovaginal cytology (1999) Arch Pathol Lab Med, 123, pp. 1079-1084Boman, F., Duhamel, A., Trinh, Q.D., Deken, V., Leroy, J.L., Beuscart, R., Evaluation of cytological screening for cancers and precancerous lesions of the cervix (2003) Bull Cancer, 90, pp. 643-647Cox, J.T., Schiffman, M., Solomon, D., 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 (2003) Am J Obstet Gynecol, 188, pp. 1406-1412. , ASCUS-LSIL Triage Study (ALTS) GroupSongveeratham, S., Kietpeerakool, C., Khunamornpong, S., Sribanditmongkol, N., Srisomboon, J., Preceding cervical cytology in women with high-grade squamous intraepithelial lesion (2011) Arch Gynecol Obstet, 283, pp. 343-348Zeferino, L.C., Derchain, S.F., Cervical cancer in the developing world (2006) Best Pract Res Clin Obstet Gynaecol, 20, pp. 339-354Wright, J.D., Grigsby, P.W., Rader, J.S., Mutch, D.G., Powell, M.A., Gao, F., Gibb, R.K., Effect of a to radical hysterectomy specimen on survival for early stage cervical cancer (2007) Gynecol Oncol, 107, pp. 280-284Walker, J.L., Wang, S.S., Schiffman, M., Solomon, D., Predicting absolute risk of CIN3 during post-colposcopic follow-up: Results from the ASCUS-LSIL Triage Study (ALTS) (2006) Am J Obstet Gynecol, 195, pp. 341-348. , ASCUS LSIL Triage Study GroupLee, K.R., Minter, L.J., Crum, C.P., Koilocytotic atypia in Papanicolaou smears. 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