Article

Hierarchical Clustering of Human Papilloma Virus Genotype Patterns in the ASCUS-LSIL Triage Study

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20852-7234, USA.
Cancer Research (Impact Factor: 9.33). 10/2010; 70(21):8578-86. DOI: 10.1158/0008-5472.CAN-10-1188
Source: PubMed

ABSTRACT

Anogenital cancers are associated with ∼13 carcinogenic human papilloma virus (HPV) types in a broader group that cause cervical intraepithelial neoplasia (CIN). Multiple concurrent cervical HPV infections are common, which complicates the attribution of HPV types to different grades of CIN. Here we report the analysis of HPV genotype patterns in the atypical squamous cells of undetermined significance-low-grade squamous intraepithelial lesion triage study with the use of unsupervised hierarchical clustering. Women who underwent colposcopy at baseline (n = 2,780) were grouped into 20 disease categories based on histology and cytology. Disease groups and HPV genotypes were clustered with the use of complete linkage. Risk of 2-year cumulative CIN3+, viral load, colposcopic impression, and age were compared between disease groups and major clusters. Hierarchical clustering yielded four major disease clusters: cluster 1 included all CIN3 histology with abnormal cytology; cluster 2 included CIN3 histology with normal cytology and combinations with either CIN2 or high-grade squamous intraepithelial lesion cytology; cluster 3 included older women with normal or low-grade histology/cytology and low viral load; and cluster 4 included younger women with low-grade histology/cytology, multiple infections, and the highest viral load. Three major groups of HPV genotypes were identified: group 1 included only HPV16; group 2 included nine carcinogenic types, plus noncarcinogenic HPV53 and HPV66; and group 3 included noncarcinogenic types, plus carcinogenic HPV33 and HPV45. Clustering results suggested that colposcopy missed a prevalent precancer in many women with no biopsy/normal histology and high-grade squamous intraepithelial lesion. This result was confirmed by an elevated 2-year risk of CIN3+ in these groups. Our novel approach to study multiple genotype infections in cervical disease with the use of unsupervised hierarchical clustering can address complex genotype distributions on a population level.

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    • "Sin lesión cervical n 1° 2° 3° 4° 5° 6° 7° 8° 9° 10° Referencia México 356 16, 62 51, 84 18 53, Cp6108 52, 70, 54, 55 Aguilar-Lemarroy et al. 2015 EU 670 16 52 54 31 18 84 51, 53 Cp6108 Wentzensen et al. 2010 Suecia 58 16,52, 56,59, 53 42 54, 61, 73 18, 39, 51, 84 31, 55, 58,62, 66 Cp6108 6, 33, 40, 45, 70, 83 35, 67, 72, 81, 82 Fröberg et al. 2008 Tanzania 148 58 66 82 26 16 18, 45 Vidal et al. 2011 Sudáfrica 23 16, 35 33, 51, 56 26, 39, 42, 53, 55, 58, 59, 61, 68, 69, 83 Marais et al. 2008 Australia 170 16 53 Cp6108 73 52 31 51 18, 39, 56, 58, 59 45, 66 35 Stevens et al. 2009 LIEBG México 315 16 84 58 59 62 18 66, 39 31, 51, 53, 70 52, 56, Cp6108 61 Aguilar-Lemarroy et al. 2015 Canadá 508 16 51 39 52 53 Cp6108 66 31, 42 18, 56 58 Coutlée F et al. 2011 EU 280 16 51 18, 53 59 39, 66 52 6 31 35, 58 33 Wentzensen et al. 2010 Suecia 39 42, 84 16, 52, Cp6108 31, 56, 61, 62, 66 35, 58, 59 6, 18, 39, 45, 51, 67, 70, 73, 83 Fröberg et al. 2008 Sudáfrica 18 35 16, 18, 45, 53, 56 51, 58, 59, 62, 66 Marais et al. 2008 Australia 196 16 31, Cp6108 51, 53 52 66 39, 56 58, 59, 6 73 45 S125 Rev Med Inst Mex Seguro Soc. 2015;53 Supl 2:S122-30 Flores-Miramontes MG et al. "

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