Christoph Schmitt

Determination of features indicating progression in atypical squamous cells with undetermined significance: human papillomavirus typing and DNA ploidy analysis from liquid-based cytologic samples.

The Bethesda System of cervical cytologic findings introduced the term ASCUS (atypical squamous cells of undetermined significance) to cover the broad zone separating normal cytomorphology from definitive squamous intraepithelial lesions (SILs). The management of patients with ASCUS is particularly problematic as approximately 10% of ASCUS patients develop SIL and 1 per 1000 develop cervical carcinoma.

Human papillomavirus typing and DNA ploidy determination of squamous intraepithelial lesions in liquid‐based cytologic samples

Infection by high‐risk human papillomavirus (HPV) plays a role in the evolution of cervical carcinoma. Cellular atypia and consecutive DNA content alterations in cytologic samples are consequences of a preexisting viral infection.

Prevalence and genotype distribution of multiple human papillomavirus infection in the uterine cervix: A 7.5-year longitudinal study in a routine cytology-based screening population in West Germany†

The availability of vaccines against certain HPV types and the development of broad spectrum genotyping methods have increased interest in co‐infections with different HPV types. In the present study, the prevalence and type‐specific composition of multiple HPV infections were investigated in a routine cervical screening population in West Germany both at a cross‐sectional level and longitudinally. Four hundred eighty‐nine out of 8,090 women were diagnosed with multiple HPV infections once or repeatedly. During the 7.5‐year study period, the cumulative prevalence of HPV co‐infections was 15.3% in contrast to the cross‐sectional prevalence of 3.8% at single visits. The overall cumulative prevalence within the cohort of all women screened was 6.9%. Using consensus PCR with sequencing and type‐specific PCRs, two to three HPV types were detected simultaneously, whereas broad spectrum methods detected up to seven different genotypes in one sample. Nevertheless, the most common pattern of co‐infection occurred with two to three HPV types irrespective of the age of the patient, cytology and histology of the lesions and the method used. The most common genotypes detected were HPV 16, 31, 53, 51, 52, and 66, and the most common pattern of co‐infection was double infection with HPV 16 and 31. These results show that rates and patterns of multiple HPV infections are largely dependent on the methodology used and the time interval between tests. Given the significance of HPV vaccination and its expected influence on immunized populations, it is essential to gain additional insights into the natural course and pathogenic effect of multiple HPV infection longitudinally. J. Med. Virol. 80:1814–1823, 2008.

Aberrant, highly hyperdiploid cells in human papillomavirus-positive, abnormal cytologic samples are associated with progressive lesions of the uterine cervix.

Infection with oncogenic‐type human papillomavirus (HPV) and consecutive cytologic abnormalities of the uterine cervix precede the evolution of carcinoma. However, the specificity of both changes is too low to predict the true malignant potential of the change in a given time point, because the majority of the HPV infections revert to normal with time. In preliminary studies, the authors demonstrated that, among many dysregulatory phenomena at the cytologic level, the occurrence of significant DNA content aberrations were in good correlation with progressive cervical changes; and, as a marker for this, the significance of cells with nuclear DNA content > 9c (9c cells) was investigated using slide‐based cytometry. The objective of the current study was to determine whether 9c cells in cytologic samples that presented with dysplasia and with high‐risk HPV types were associated with the development of higher grade cervical intraepithelial neoplasia (CIN II+).

A 7.5-year prospective study of longer than 18 months type-specific human papillomavirus persistence in a routine cytology-based cervical screening population of about 31 000 women in West Germany.

The objective of this study was to analyse the prevalence, infection pattern, duration and outcome of long-term, type-specific, persistent human papillomavirus (HPV) infections in a routine cytology-based cervical screening population of West German women followed up for 7.5 years. From a screening population of 31 000 women, a strictly selected cohort of 100 patients with ≥18-month persistent, type-specific HPV infection were prospectively followed up for a mean of 35.52 months (±13.0). HPV type prevalence and odds ratios for regression, progression and steady state were analysed, as well as the influence of age and HPV coinfection on outcome. Altogether, 21 different genotypes were detected. Seventy-two percent of women were infected with high-risk HPVs, 24% with low-risk and 4% with unknown risk HPV types; 44% of cases had coinfections with multiple HPV types. The risk of progression in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions was the highest for infections with high-risk HPVs [odds ratio: 2.2 (0.79–6.11, 95% confidence interval)], whereas cases with low-risk and unknown risk HPVs tended to regress or remained unchanged during follow-up. The mean duration of infections showed considerable variation among the different HPV types and risk groups detected and ranged between 19.7 and 54.3 months. Age was not significantly associated with disease progression and infection duration, and histology had a poor sensitivity for detecting high-grade dysplasia. In conclusion, detecting long-term persistent HPV infections by genotyping may help to identify women with cervical intraepithelial lesions who are at lower and higher risk of developing high-grade precancer and cancer. This may influence future screening strategies and therapy decisions.