Genital warts in children: what do they mean?

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© 2012 Dr. Yasmin Leela JayasinghePublications included in thesis:Jayasinghe, Y. L., Moore, E. E., Tabrizi, S. N., Grover, S. R. & Garland, S. M. (2013). Human papillomavirus in adolescents: lessons learned from decades of evaluation. Journal of Paediatrics and Child Health, 49(2), 99-104. DOI: 10.1111/j.1440-1754.2011.02073.xJayasinghe, Y. & Garland, S. (2008). Cancers related to human papillomavirus in adolescent females. In M. Moorland (Ed.), Cancer in Female Adolescents (pp. 59-102). New York: Nova.Jayasinghe, Y. & Garland, S. (2006). Genital warts in children: what do they mean? Archives of Disease in Childhood, 91(8), 696-700. DOI: 10.1136/adc.2005.092080International recommendations suggest delayed onset of cervical cytology screening. This may raise concern for perceived high risk women, including sexual abuse victims. However risk for early development of cervical carcinoma (CC) is unknown. This thesis will shed light on virological or environmental risk factors for early onset cervical disease (EOCD: CC, cervical intraepithelial neoplasia 3, adenocarcinoma in situ), in women ≤ 25 years. This could inform cervical screening and human papillomavirus (HPV) vaccination strategies. In Section 1, morphology, survival, HPV genotypes and HPV 16 variants (in E6, E2, L1 genes) in women ≤ 25 years with CC (cases), was compared to women diagnosed >25 years (controls), between 1983-2007. Median age of CC diagnosis in cases was 24 years, with 39% diagnosed at 25 years. Squamous cell carcinoma (SCC) accounted for 61% of cases and adenocarcinoma (AC) 23%, and was not significantly different from controls. Microinvasive cancers were more common in cases. Cases had significantly better survival, however survival advantage was lost for AC or less common morphological types, advanced stage and high grade disease. There was heterogeneity of disease in young women. In cases diagnosed at 25 years, 82% had SCC (representing the beginning of the age-incidence curve for SCC with good prognosis) and 5% had AC; whereas for cases diagnosed ≤ 24 years, 34% had AC with equivalent survival to controls. HPV 18 was more common in cases than controls. In cases with early stage disease, HPV 18 conferred poorer prognosis, compared to non-HPV 18 genotypes. HPV 16 or 18 was found in 88% of cases, suggesting the currently licensed vaccines should, with widespread coverage, be highly efficacious for young people, provided administration prior to infection. The proportion of HPV 16 variants did not differ between groups. European variants accounted for 88% of HPV 16 positive CC in the study population. There was no significant difference in genomic variability between cases and controls for E6, E7, or L1 genes. L1 variants were highly conserved and unlikely to affect HPV vaccine immunogenicity. Controls had a higher proportion of amino acid changes compared to cases, but it is unclear if this confers any protection from rapid-onset disease. In Section 2 a self-administered postal survey was sent to women with EOCD diagnosed from 1983-2007, and matched control groups (including women attending a Well Women’s Clinic [WW]), to estimate risk of EOCD associated with childhood sexual abuse (CSA), unwanted adolescent sexual activity (UASE), sexual, reproductive and lifestyle factors. Cases had higher-risk sexual-reproductive profiles than controls. CSA was experienced in 23% of all participants and associated with known risk factors for CC. Cases with CC (but not insitu disease) had a higher proportion of severe forms of CSA or UASE compared to WW. Median age of penile-genital abuse was 10 years. Findings support vaccination within forensic protocols, identification and earlier vaccination of high-risk youth (wards of the state, institutionalised youth), and continued cervical screening from 18 years in sexual violence victims. This is the first study investigating the effect of sexual violence on EOCD.Restricted Access: This resource is not available from the Digital Repository for copyright reasons. This is a citation and abstract only record