Human papillomavirus (HPV) genotype distribution in invasive cervical cancers in France: EDITH study

Abstract

Invasive cervical cancer (ICC) remains a significant cause of morbidity and mortality in France. Since human papillomavirus (HPV) is the necessary cause of ICC, the aim of this study was to assess the type-specific prevalence of HPV in ICC in France in order to locally evaluate the potential benefit of an HPV 16/18 L1 virus-like particles (VLP) vaccination. A total of 516 histological specimens collected in 15 centers were analyzed. Among them, 86% had a diagnosis of squamous cell carcinoma (SCC) whereas 14% were adenocarcinomas (ADC). HPV genotyping was performed using the INNO-LiPA assay allowing the specific detection of 24 HPV genotypes both high risk (HR) and low risk (LR). The overall HPV prevalence in ICC was 97%. The most prevalent genotypes were HPV 16 (73%) and HPV 18 (19%) followed by HPV 31 (7%), 33, 68, 45, 52 and 58 (4.1-2.3%). HPV 16 and/or 18 were associated with 82% of ICC, 10% being HPV 16 and 18 coinfections. While HPV 16 was the most prevalent type in both SCC (74%) and ADC (64%), HPV 18 was by far more prevalent in ADC (37%) compared to SCC (16%; p < 0.001). Multiple infections with at least two different HR HPV genotypes were observed in 22% of ICC. Given the high HPV 16/18 prevalence and taking into account possible production of crossneutralizing antibodies against other HPV types, HPV 16/18 L1 VLP vaccination would be expected to significantly reduce the burden of ICC in France. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; invasive cervical cancer; prevalence; genotype Despite widespread screening, invasive cervical cancer (ICC) remains a significant cause of morbidity and mortality and represents the second most common cancer among women worldwide. 1In France, this cancer accounts for 3,400 new cases and about 1,000 deaths annually. 2,3 It is universally accepted that human papillomavirus (HPV) is the necessary cause of ICC with more than 99% of ICC containing the DNA of the virus. 4 HPV is sexually transmitted and the majority of infections occurs in adolescents or young adults with the highest prevalence observed in the 15 to 19-year-old group.5 After infection, spontaneous viral clearance is observed in most cases within a year and time to clearance is likely to depend on HPV genotype. It has been observed, for example, that HPV 16 persisted longer than other genotypes.6 HPV persistence represents the major risk factor for cervical cancer.6-8 After established infection, mild cervical abnormalities may appear. These abnormalities spontaneously resolve if HPV is eliminated, but may progress to low and high grade cervical intraepithelial neoplasia (CIN 1 and CIN 2/3, respectively) and ICC in case of viral persistence. About 40 different HPV types are known to infect the genital tract of which 15, known as ''high risk'' (HR) types, have been associated with ICC.10 Among these HR types, HPV types 16 and 18 are responsible for about 70% of ICC worldwide 11 and 60-70% of high grade lesions according to geographical area considered.12 Prophylactic vaccines based on HPV 16/18 L1 ...

Prevalence of Human Papillomavirus Types in High-Grade Cervical Intraepithelial Neoplasia and Cancer in Italy

“…Consequently, in a context of high Pap test coverage, lesions undetected by screening controls are more likely to be HPV16 or HPV18. This interpretation is consistent with the observation that the proportion of HPV16/18 in cancers is higher in high-income countries [Western Europe (45) and North America] with large diffusion of the Pap test and lower in low/middle-and lowincome countries (South America, Asia, and Africa; ref. 13).…”

“…GP5+/GP6+ primers amplify a broad spectrum of HPV genotypes by targeting a 150-bp fragment within the L1 open reading frame of the HPV genome (31). All samples and controls, independent of gel results, were subjected to the reverse line blot (RLB) for detection of 12 high-risk HPV types (16,18,31,33,35,39,45, 51, 52, 56, 58, and 59), 1 probably carcinogenic HPV type (68), and 5 possibly carcinogenic HPV types (26, 53, 66, 73, and 82; ref. 32).…”

Analysis of Human Papillomavirus Type 16 (HPV16) DNA Load and Physical State for Identification of HPV16-Infected Women with High-Grade Lesions or Cervical Carcinoma

“…Based on our results, we propose that among HR-HPV infected women, those with an HPV16 load of above 22,000 copies/10 3 cells or with an E2/E6 ratio below 0.5 are likely to present a high-grade lesion. These cutoff values, however, are relevant for HPV16 only, which is detected for 34 to 52% of patients with CIN2/3 and for 52 to 58% of cancers (4, 10, 34, 48) (62% of CIN2/3 and in 73% of cancers in France [42,43]). Because other HR-HPVs (e.g., HPV18, HPV31, and HPV45) are also responsible for cervical lesions, relevant cutoffs should be determined for these genotypes.…”

Comparison of the clinical performance of carcinogenic HPV typing of the Linear Array and Papillocheck® HPV-screening assay

“…26,27 The IARC pooled analysis of 3085 invasive cervical carcinomas revealed that the five most common HPV genotypes were, in descending order of frequency, HPV16, 18, 45, 31, and 33. 10 In our study, these genotypes were detected in 74% of the cases.…”