HPV16/18 genotyping for the triage of HPV positive women in primary cervical cancer screening in Chile

Infectious Agents and Cancer

Catterina Ferreccio²  Martha Pruyas⁴  María Isabel Barriga⁵  Paola Viviani¹  Paz Cook¹  Helena Poggi³  Vanessa Van De Wyngard¹  Marcela Lagos³ 

[1] Departamento de Salud Pública, Escuela/Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 434, Santiago 8330073, Chile;Advanced Center for Chronic Diseases (ACCDis), Sergio Livingstone 1007, Independencia, Santiago 8380492, Chile;Departamento de Laboratorios Clínicos, Facultad de Medicina, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4686, Macul, Santiago 7820436, Chile;Departamento de Anatomía Patológica, Hospital Dr Sótero del Río, Av. Concha y Toro 3459, Puente Alto, Santiago 8207257, Chile;Departamento de Obstetricia y Ginecología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Lira 85, Santiago 8330074, Chile

关键词: Triage;    Genotype;    HPV 18;    HPV 16;    HPV DNA testing;    Human papillomavirus;    Cervical cancer screening;   

Others  :  1234408
DOI  :  10.1186/s13027-015-0038-5

 received in 2015-05-07, accepted in 2015-10-07,  发布年份 2015

【 摘 要 】

Background

We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants.

Methods

Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test).

Results

Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %.

Conclusions

HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.

【 授权许可】

   
2015 Lagos et al.

【 图 表 】

Fig. 1.

【 参考文献 】

• [1]Chile Ministry of Health, Departamento de Estadisticas e Informacion de Salud. http://www.deis.cl/wp-content/uploads/2012/11/CoberturaPAP_Oficial_Region2010_2011.pdf (in Spanish; accessed 17 October 2014).
• [2]Chile Ministry of Health, Departamento de Estadisticas e Informacion de Salud. http://deis.minsal.cl/vitales/vitales2010/Serie_Mortalidad_causa_Chile_2000_2010/Chile.htm (in Spanish; accessed 17 October 2014).
• [3]Ferreccio C, Barriga MI, Lagos M, Ibanez C, Poggi H, Gonzalez F, Terrazas S, Katki HA, Nuñez F, Cartagena J, Van De Wyngard V, Viñales D, Brañes J: Screening trial of human papillomavirus for early detection of cervical cancer in Santiago, Chile. Int J Cancer 2013, 132(4):916-23.
• [4]Arbyn M, Ronco G, Anttila A, Meijer CJLM, Poljak M, Ogilvie G, Koliopoulos G, Naucler P, Sankaranarayanan R, Peto J: Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine 2012, 30S:F88-99.
• [5]Ronco G, Dillner J, Elfström KM, Tunesi S, Snijders PJF, Arbyn M, et al.: Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014, 383:524-32.
• [6]de Sanjose S, Quint WGV, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, Vallejos CS, Alonso de Ruiz P, et al.: Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol 2010, 11:1048-56.
• [7]Li N, Franceschi S, Howell-Jones R, Snijders PJF, Clifford GM: Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: variation by geographical region, histological type and year of publication. Int J Cancer 2011, 128:927-35.
• [8]Khan MJ, Castle PE, Lorincz AT, Wacholder S, Sherman M, Scott DR, Rush BB, Glass AG, Schiffman M: The elevated 10-Year Risk of Cervical Precancer and Cancer in Women With Human Papillomavirus (HPV) Type 16 or 18 and the Possible Utility of Type-Specific HPV Testing in Clinical Practice. J Natl Cancer Inst 2005, 97:1072-9.
• [9]Bulk S, Bulkmans NWJ, Berkhof J, Rozendaal L, Boeke AJP, Verheijen RHM, Snijders PJF, Meijer CJLM: Risk of high-grade cervical intra-epithelial neoplasia based on cytology and high-risk HPV testing at baseline and at 6-months. Int J Cancer 2007, 121:361-7.
• [10]Kjaer SK, 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. J Natl Cancer Inst 2010, 102:1478-88.
• [11]Clifford GM, Smith JS, Aguado T, Franceschi S: Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Brit J Cancer 2003, 89:101-5.
• [12]Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, Clifford GM: Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update. Int J Cancer 2007, 121:621-32.
• [13]Benoy IH, Broeck DV, Ruymbeke MJ, Sahebali S, Arbyn M, Bogers JJ, et al.: Prior knowledge of HPV status improves detection of CIN2 by cytology screening. Am J Obstet Gynecol 2011, 205:569.e1-7.
• [14]Wright TC, Stoler MH, Behrens CM, Apple R, Derion T, Wright TL: The ATHENA human papillomavirus study: design, methods, and baseline results. Am J Obstet Gynecol 2012, 206:46.e1-11.
• [15]Ili CG, Brebi P, Lopez J, Garcia P, Leal P, Suarez E, Roa JC: Genotyping of Human papillomavirus in Cervical Intraepithelial Neoplasia in a High-Risk Population. J Med Virol 2011, 83:833-7.
• [16]Castle PE, Stoler MH, Wright TC, Sharma A, Wright TL, Behrens CM: Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol 2011, 12:880-90.
• [17]Rijkaart DC, Berkhof J, van Kemenade FJ, Coupe VMH, Hesselink AT, Rozendaal L, Heideman DAM, Verheijen RH, Bulk S, Verweij WM, Snijders PJF, Meijer CJLM: Evaluation of 14 triage strategies for HPV DNA-positive women in population-based cervical screening. Int J Cancer 2012, 130:602-10.
• [18]Naucler P, Ryd W, Törnberg S, Strand A, Wadell G, Elfgren K, Rådberg T, Strander B, Forslund O, Hansson BG, Hagmar B, Johansson B, et al.: Efficacy of HPV DNA Testing With Cytology Triage and/or Repeat HPV DNA Testing in Primary Cervical Cancer Screening. J Natl Cancer Inst 2009, 101:88-99.
• [19]Castle PE, Lorincz AT, Mielzynska-Lohnas I, Scott DR, Glass AG, Sherman ME, Schussler JE, Schiffman M: Results of Human Papillomavirus DNA Testing with the Hybrid Capture 2 Assay Are Reproducible. J Clin Microbiol 2002, 40:1088-90.
• [20]Godinez JM, Tous S, Baixeras N, Moreno-Crespi J, Alejo M, Lejeune M, Bravo IG, Bosch FX, de Sanjose S: Performance of the digene LQ, RH and PS HPVs genotyping systems on clinical samples and comparison with HC2 and PCR-based Linear Array. Infect Agents Canc 2011, 6:23. BioMed Central Full Text