Chromosomal profiles of high-grade cervical intraepithelial neoplasia relate to duration of preceding high-risk human papillomavirus infection.

High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behavior and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5-year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI). For comparison, six CIN3 adjacent to squamous cell carcinomas (CIN3-SCC), the corresponding SCCs, and six CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≥5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≥5yrPHI, all except one CIN3-SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≥5yrPHI compared to <5yrPHI was highly significant (p = 0.001), suggesting that CIN3≥5yrPHI represent more severe lesions. In conclusion, longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short-term risk of cervical cancer.

HPV-associated flat penile lesions in men of a non-STD hospital population: less frequent and smaller in size than in male sexual partners of women with CIN.

Human papillomavirus (HPV) infections and HPV-associated penile lesions are frequently found in male sexual partners of women with cervical intraepithelial neoplasia (CIN). To determine the significance of these findings, we studied the prevalence of HPV and HPV associated penile lesions in a male hospital population with non-STD complaints. Penoscopy was performed after application of acetic acid to identify flat lesions, papular lesions, condylomata acuminata and pearly penile papules (PPPs). Presence of HPV DNA in penile scrapes was tested by GP5+6+ PCR. In case of HPV 16 positivity, viral loads were quantified using a LightCycler based real-time PCR method. Comparing the non-STD male hospital population (n = 118) with the male sexual partners of women with CIN (n = 238), flat penile lesions were found in 14% vs. 60% and penile HPV in 25% vs. 59% of the men, respectively. We found that the presence of penile HPV and, in case of HPV 16 positivity, higher viral loads were associated with the presence of flat penile lesions. Amongst the HPV-positive men, flat penile lesions were more common and larger in size in male sexual partners of women with CIN than in the non-STD hospital population. HPV infections and HPV-associated flat penile lesions are commonly found in the non-STD male population. However, these lesions are less frequently present and smaller in size than in male sexual partners of women with CIN. Higher viral loads in penile scrapes of male sexual partners of women with CIN are reflected by a higher prevalence of flat penile lesions and a larger size of these lesions.

Myocilin mutations in a population-based sample of cases with open-angle glaucoma: the Rotterdam Study.

PURPOSE: To investigate the prevalence of myocilin (MYOC) mutations in a population-based sample of open-angle glaucoma (OAG) cases and to describe a family with both juvenile and adult onset OAG caused by a mutation in MYOC. METHODS: MYOC was screened in cases derived from the Rotterdam Study in the Netherlands. Definite OAG was defined as a glaucomatous optic neuropathy together with a glaucomatous visual field defect. Upon the identification of the Asn480Lys mutation in one case, seven additional family members were studied. To test for a founder effect with earlier reported families with this mutation, the haplotypes of MYOC flanking markers D1S2851, D1S242, D1S218, and D1S1165 were compared. RESULTS: Seven sequence alterations in MYOC were found in 14 of 47 OAG cases; six of these were also found in controls. In one case, an Asn480Lys mutation was found. In relatives of the latter patient, the phenotype ranged from a glaucomatous optic neuropathy without visual field defect in a 70-year-old patient to severely affected optic discs and a remaining temporal remnant in a 34-year-old patient; those without the mutation had no signs of OAG. Haplotype analysis suggested a different origin of the mutation. CONCLUSIONS: The prevalence of MYOC mutations (2.2%) was similar to that found in hospital-based studies. Although mutations in MYOC are rare, relatives carrying this mutation run a high risk of developing the disease. Instead of submitting all members of a family with the Asn480Lys mutation to frequent follow-up, medical care can be restricted to those carrying the mutation.