Presence of E6 and E7 mRNA from Human Papillomavirus Types 16, 18, 31, 33, and 45 in the Majority of Cervical Carcinomas

Abstract

The oncogenic potential of the human papillomavirus (HPV) early genes E6 and E7 is well established and a source of interest with regard to HPV testing for cervical carcinoma. Here we present a study performed with 204 histologically confirmed invasive cervical squamous cell carcinomas (SCCs) in which we evaluated the HPV E6 and E7 mRNA detection assay PreTect HPV-Proofer for detection of high-risk HPV types 16, 18, 31, 33, and 45. For further evaluation, detection of E6 and E7 mRNA from HPV types 35, 52, and 58 by real-time multiplex nucleic acid sequence-based amplification was also included. For comparison and to assess the overall prevalence of various HPV types, samples were also tested for HPV DNA by both consensus and type-specific PCR, reverse line blotting, sequencing, and in situ hybridization. The overall prevalence of HPV was 97%. HPV E6 and E7 transcripts were detected in 188 of 204 (92%) biopsy specimens, of which 181 contained one of the following HPV types: 16, 18, 31, 33, or 45. Consensus PCR and type-specific PCR detected HPV in 187 of 204 and 188 of 204 (92%) specimens, respectively. In conclusion, this study verifies the presence of HPV E6 and E7 mRNA in SCCs and demonstrates that HPV infections among Norwegian women with SCCs are limited mainly to the five high-risk types, 16, 18, 31, 33, and 45. This, together with the fact that PreTect HPV-Proofer detects the HPV oncogenic transcripts, suggests that the assay is a valuable approach in the field of HPV detection in cervical carcinoma.The presence of human papillomavirus (HPV) infection in the majority of cases of cervical neoplasia has been considered evidence of an etiological role of HPV in cervical cancer. The association is strong, consistent, and specific to a limited number of viral types (2,5,32,46). On the other hand, the lifelong risk of HPV infection is 80%, and only a small proportion of women infected with HPV will develop high-grade cervical neoplasia (42). Among HPV-positive women, it is therefore of the utmost importance to identify those with an increased risk of developing cervical carcinoma by either methods that reveal persistent HPV infection (38), methods that detect viral oncogene expression (40), or the use of additional human markers for cervical carcinogenesis (45).The most frequent HPV types found in cervical intraepithelial neoplasia and squamous cell carcinoma (SCC) are HPV type 16 (HPV-16) and HPV-18, which in 1995 were classified as human carcinogens by the International Agency for Research on Cancer. In total, based on their high frequencies in carcinomas, 13 HPV types are now considered carcinogenic types (6). In the largest multinational studies performed so far, HPV types 16, 18, 31, 33, and 45 were shown to be the most prevalent types associated with cervical carcinomas (2, 22, 32), with HPV-16 alone found in more than 50% of the cases. The oncogenic potential of these high-risk HPV types lies in the oncoproteins E6 and E7, which bind to and modulate a number of different gene products, in particular, the ...

A comprehensive evaluation of the accuracy of cervical pre-cancer detection methods in a high-risk area in East Congo

“…There are also strong indications that the same five types are the most predominant ones in cervical carcinomas in the rest of the world (Munoz et al, 2004;Smith et al, 2007). In a previous study, mRNA transcripts from these five types were detected in 89% of HPV-positive biopsies of cervical squamous cell carcinomas (88% by type-specific PCR) (Kraus et al, 2006).…”

Type‐specific human papillomavirus oncogene messenger RNA levels correlate with the severity of cervical neoplasia

“…About 3,800 bp length of the E6/E7/E1/E2 regions of HPV 6,11,16,18,31,33,39,45, 51, 52, 56, 58, 59 and 68 genomes from clinical samples were separately cloned into pGEM T-Easy vector (Promega) and sequenced by automated sequencing for verification of the sequences. All the type-specific primer pairs were checked by chessboard test to confirm their specificity.…”

“…[8][9][10][11][12][13][14][15] On the other hand, the occurrence of infection with HPV types 52 or 58 is relatively uncommon in cervical cancer in the Americas, Europe, Africa and Southeast Asia. 1 The presence of HPV types 16,18,31,33 and 45 E6 and E7 mRNA is found in the majority of cervical carcinomas. 16 However, the importance and prevalence of HPV 52 and 58 transcripts in normal populations and preinvasive and cervical cancers in different geographic areas such as Taiwan and other Asian countries have not been explored.…”

“…1 The presence of HPV types 16,18,31,33 and 45 E6 and E7 mRNA is found in the majority of cervical carcinomas. 16 However, the importance and prevalence of HPV 52 and 58 transcripts in normal populations and preinvasive and cervical cancers in different geographic areas such as Taiwan and other Asian countries have not been explored.…”

“…The HPV types 16,18,31,33 and 45 are reportedly the most prevalent types associated with cervical cancer worldwide. 1,5 The most common oncogenic HPV type in preinvasive and cervical cancer is HPV 16, which is detectable in 21% of women with low-grade squamous intraepithelial lesions (LSILs), 6 in more than 50% of women with cervical intraepithelial neoplasia grade 3 (CIN 3) and in women with cervical cancer in America and Europe.…”