Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe.

Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical specimens dated 2001-2008. The pooled prevalence of individual HPV types was estimated using meta-analytic methods. A total of 3,103 women were diagnosed with HG-CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV-positive, respectively. The most common HPV types in women with HG-CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both HG-CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG-CIN and associated with a high median age of HG-CIN, with a narrow age interval between HG-CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45-related cervical lesions.

HPV-type distribution and reproducibility of histological diagnosis in cervical neoplasia in Poland.

This study was performed to assess attribution of high grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) to human papillomavirus (HPV) genotypes and secondarily to assess reproducibility of HG-CIN/ICC diagnosis obtained in Poland. Formaldehyde fixed, paraffin embedded blocks of HG-CIN/ICC from two distant institutions were sent to a central laboratory together with original histological diagnoses. Central/expert review of histopathological specimens was performed and agreement between local and central/expert diagnoses was calculated. HPV detection and genotyping in the samples was carried out with the use of SPF10-LiPA25 technology. Results were analyzed for 205 HG-CIN and 193 ICC cases with centrally confirmed diagnoses. Kappa coefficients and 95 % confidence intervals for HG-CIN and ICC diagnoses were: 0.13 (0.09;0.17) and 0.19 (0.11;0.26) respectively. Cohen's kappa coefficients for lesions with representative number of samples ranged from 0.01 for cervical intraepithelial neoplasia grade 2 to 0.75 for adenocarcinoma. HPV DNA was detected in 96.1 and 91.2 % of the confirmed HG-CIN and ICC specimens respectively. HPV positive HG-CIN was most commonly attributed to HPV types: 16 (62.8), 33 (7.8), 31 (6.6), 52 (3.7), 45 (2.6) and 58 (2.6 %). HPV positive ICC was most commonly attributed to HPV types: 16 (72.1), 18 (10.8), 33 (5.7), 45 (3.4) and 31 (1.7 %). Reproducibility of histological diagnosis of HG-CIN/ICC obtained in Poland generally increases with the severity of lesion and is lowest for cervical intraepithelial neoplasia grade 2 and highest for adenocarcinoma. Over 80 % of ICC cases are vaccine-preventable in Poland.

Human papillomavirus in high-grade cervical lesions: Austrian data of a European multicentre study.

BACKGROUND: The purpose is to present the Austrian data of an observational, cross-sectional, multicentre study conducted in 13 European countries. This study was undertaken to assess human papillomavirus (HPV) type distribution in high-grade cervical lesions. METHODS: Two hundred and ninety cases of high-grade cervical intraepithelial neoplasia (CIN2, CIN3) or adenocarcinoma in situ of the cervix from 2004 to 2007 were analysed by histopathological review and polymerase chain reaction for HPV. RESULTS: Two hundred and nine cases were "histologically eligible" and of those 206 were HPV+. Median age was 34 years (19-76 years). CIN3 was the most frequent diagnosis (64.6 %), followed by CIN2/3 (19.4 %) and CIN2 (13.6 %). Adenocarcinoma in situ was only detected together with a squamous lesion in 2.4 % cases. Majority of women (75.2 %) were infected with a single HPV type, 98.1 % of them with high-risk HPV types: HPV 16 (56.1 %), HPV 33 (12.3 %), HPV 31 (11.0 %), HPV 18 (3.9 %), HPV 35 (3.9 %), HPV 51 (3.2 %) and HPV 52 (2.6 %), HPV 58 (1.9 %) and HPV 45 (0.6 %). The low-risk HPV 6 was found in 1.3 % cases. Forty-six lesions (22.3 %) contained multiple infections, 71.1 % of those were HPV 16 or 18 and 91.1 % were HPV 16, 18, 31, 33 or 45 positive. CONCLUSIONS: These Austrian data clearly demonstrate that HPV 16 is the predominant type in high-grade CIN, the immediate precursor lesions of cervical cancer. More than 60 % of the lesions were associated with HPV 16 and 18 and more than 85 % with HPV 16, 18, 31, 33 or 45. The prevalence of adenocarcinoma in situ is underestimated, since its detection is difficult with the current cytology screening.

Cervical cancers associated with human papillomavirus types 16, 18 and 45 are diagnosed in younger women than cancers associated with other types: a cross-sectional observational study in Wales and Scotland (UK).

BACKGROUND: Most cervical cancers are attributable to infection with one of fourteen types of human papillomavirus (HPV), but HPV types differ in oncogenic potential. Characterisation of cancers associated with specific HPV types is required to predict the likely impact of current prophylactic vaccines and the potential benefits of vaccine formulations including additional HPV types. OBJECTIVE: The study aimed to correlate HPV type with histology and age at diagnosis, in Invasive Cervical Cancers (ICCs) from two of the devolved countries of the UK (Wales and Scotland). STUDY DESIGN: Centralised histopathology review and rigorously standardised HPV-DNA typing were applied to 592 ICC diagnosed 2001-2006. HPV status was analysed in relation to histology and age at diagnosis. RESULTS: HPV infection was confirmed in 535/592 cases. Among the 497 tumours infected with single HPV types, the three most common types were HPV16 (62% 95%CI: 57.6-66.1), HPV18 (18.9% 95%CI: 15.7-22.6) and HPV45 (5.4% 95%CI: 3.7-7.8). HPV16 or 18 were present in 80.9% of HPV positive cases. Women with tumours associated with HPV types 16, 18 and 45 were on average 10.5 years younger at diagnosis than women with tumours associated with other HPV types. CONCLUSIONS: Prophylactic vaccines targeting HPV16 and 18 could potentially prevent up to 80.9% of ICC in the populations investigated. Cancers associated with HPV16, 18 and 45 were diagnosed at younger ages, supporting the hypothesis of faster progression than for tumours caused by other HPV types.