HPV testing in the follow-up after treatment of women with CIN.

Department of Gynecologic Oncology, Charité Universitätsmedizin Berlin, Campus Mitte und Benjamin Franklin, Germany Hindenburgdamm 30, 12200 Berlin.
Gynecologic Oncology (Impact Factor: 3.93). 11/2007; 107(1 Suppl 1):S5-7. DOI: 10.1016/j.ygyno.2007.07.048
Source: PubMed
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    ABSTRACT: The aim of study was to investigate factors predicting persistence or relapse of disease after cervical conisation for high-grade squamous intraepithelial lesions (CIN 2 or 3). The study involved 78 women with high-grade squamous intraepithelial lesions, conservatively treated with loop electroexcision procedure for cervical conisation and subsequent with CO(2) laser-vaporisation of the cervical bed. Histological specimens were totally included and examined by an experienced pathologist. To evaluate the efficacy of treatment, the patients were examined with colposcopy and Pap smear 4 months after surgery and with PCR to search for and genotyping of HPV, 10 months after treatment. During the post-treatment follow-up, the cytologic examination showed persistent/relapsing disease in six patients (7.6%). In only 1 case, the deep margin of the cone was considered positive for CIN (16%).Ten months after treatment, viral typing revealed the persistence of high-risk HPV in all of these patients. Conversely, the viral follow-up of the other 72 patients without persisting/relapsing disease after treatment disclosed low-risk HPV genotypes in 6 cases, high-risk HPV in 2 cases (2.7%), whereas 7 cases had positive margins for CIN (9.7%). The risk of persistence and relapse of CIN in the group with positive margins was not statistically significant (P = 0.87), whereas it was in the group with HR-HPV positive (P = 0.000048). HPV testing is the most sensitive mean of identifying persistence or relapse early and is therefore capable of optimising follow-up after the treatment of high-grade CIN.
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    ABSTRACT: Host genetic characteristics and environmental factors may correlate with risk for cervical cancer development. Here we describe a retrospective screening study for single nucleotide polymorphisms (SNPs) in genetic markers TP53, MTHFR, CYP1A1, and CYP2E1 in 749 patients. A multiplex ligation-dependent polymerase chain reaction approach was applied. We used archived material from human papillomavirus tests and correlated SNP genotypes to the corresponding clinical data. Semantic integration was used to identify and evaluate the clinical status from electronic health records. An association with cervical cancer and high-grade dysplasia was found for the rare homozygous CC genotype (rs4646903) in CYP1A1 (odds ratio [OR], 8.862). Odds ratios were also significantly elevated for heterozygous MTHFR CT genotype (rs1801133; OR, 1.457). No significant association was found in TP53 (rs1042522) and CYP2E1 (rs3813867). In addition, we found smokers at higher risk (OR, 2.688) and identified pregnancies as a significant risk factor (OR, 1.54). Our protocol enables a feasible way for further retrospective large sample size evaluation of potential genetic markers. This study revealed genetic associations of a rare SNP genotype with cervical dysplasia in one of the largest patient sample to date that warrants further investigation.
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    ABSTRACT: Expression of high-risk HPV oncogenes results in a strong overexpression of cellular protein p16(INK4a). Immunohistochemical staining for p16(INK4a) is widely used as diagnostic marker. However, p16(INK4a) upregulation was also described as a biomarker of age. Here we analyzed p16(INK4a) expression in cervical smears to investigate if patient age may influence p16(INK4a)-based cervical cancer diagnosis. p14(ARF) was analyzed as a related supportive biomarker. Cervical scrapes were taken and stored in RNAlater. Total RNA was extracted, and cDNA was analyzed for expression of p16(INK4a) and p14(ARF) relative to β-actin, by real-time reverse transcriptase PCR SYBR-Green I assays. Patient-derived smears referred as HSIL (n=45) had 6.27-fold higher p16(INK4a) mRNA expression than smears of cytologically normal and HPV-negative persons (n=48). Expression of p14(ARF) was 4.87-fold higher. When women with normal diagnoses were stratified for age, a significantly enhanced p16(INK4a) (2.88-fold) and p14(ARF) (1.9-fold) expression was observed as a consequence of ageing. A significant age-dependent upregulation was also observed in older HSIL patients (2.54-fold). Our study revealed significantly enhanced expression of p16(INK4a)/p14(ARF) mRNA in cervical scrapes referred to as HSIL compared with normal women. An age-dependent bias has to be considered when quantifying these tumor suppressor genes, with respect to cervical cancer development.
    Modern Pathology 11/2011; 25(3):465-70. · 5.25 Impact Factor


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May 20, 2014