Type of human papillomavirus is related to clinical features of cervical carcinoma

Key words: human papillomavirus infection; cervical cancer, epidemiology; ChinaThere is strong epidemiologic evidence indicating that human papillomavirus (HPV) plays a central role in the etiology of cervical cancer. [1][2][3][4] The women positive for HPV DNA have a risk of developing cervical cancer 15-50 times higher than those without HPV DNA. 1,2,4,5 Although HPV infection is common among young women, only a small minority go on to develop cervical cancer. This situation was reviewed by a group of researchers, who concluded that viral persistence of oncogenic HPV appears to be crucial for the development of cervical cancer. 6 Indeed, HPV-16, -18, -31 and -33 have been officially declared to be oncogenic by the World Health Organization (WHO). 7 The International Biological Study on Cervical Cancer (IBSCC) study group revealed that on average 92.9% of the tumors contained HPV DNA, with a range of 75-100%. 8 Although this international survey included 10 of the 18 regions of the world and provided the most extensive global view of HPV in cervical cancer, there were no data from China, 1 of the largest populations in the world. Furthermore, there are few published data from a well-designed study using a quality-controlled method on the prevalence of either HPV infection or HPV genotypes in cervical cancers in China.We conducted a multicenter study of HPV infection in cervical cancer by selecting 5 geographic regions of China: Shanghai (Eastern China), Guangzhou (Southern China), Sichuan (Western China), Beijing (Northern China) and Hong Kong (Specific Administration Region). MATERIAL AND METHODS PatientsCervical cancer specimens were collected from each of the 5 regions in China, including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. Each of the 5 settings (Tumor Hospital, Shanghai Medical University in Shanghai, Tumor Hospital, Sun Yat-sen University of Medical Sciences in Guangzhou, Second Hospital, West China Medical University in Sichuan, Tumor Hospital, Chinese Academy of Medical Sciences in Beijing, and Prince of Wales Hospital, The Chinese University of Hong Kong in Hong Kong) was responsible for collecting 150 or more tumor specimens consecutively from the year 1997 to 1999. Patients from Hong Kong were prospectively recruited with informed consent, and all specimens were freshly frozen. Those specimens collected in other parts of China were paraffin-embedded and retrieved retrospectively from the pathology files in those reference centers. Ethical approvals were obtained from each of the ethical review boards of the respective institutes. Histology reviewAll histologic slides submitted were reviewed by 1 of the investigators (M.K.M.C.) to reestablish the histologic type and

Section: Resultsmentioning

confidence: 62%

Prevalence of human papillomavirus in cervical cancer: A multicenter study in China

Wong

Chan

et al. 2002

“…[12][13][14][15][16][17] The presence of HPV type 18 has been identified as a predictor of early recurrence and poor survival. [5][6][7][8] A recent study found improved survival in patients with HPV 58 positive tumors. 33 The impact of multiple HPV infection, however, was not investigated.…”

Section: Discussionmentioning

confidence: 99%

“…32 According to the manufacturer's information, the biotinylated type-specific ISH probes were selected for minimal cross-hybridization with other HPV-types. Using non-radioactive Southern blot hybridization at high stringency against 100 ng of cloned HPV DNA from types 6,11,16,18,30,31,33,35,45, 51 and 52 these probes were specific for HPV 16, 18, 31 and 33, respectively, without cross-reaction with the other HPV-types. These probes did also not react with normal human nuclear DNA when probed by ISH, or with E. coli DNA when tested by dot blot hybridization.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

“…4 Studies analyzing the relationship between HPV type and prognosis in patients with cervical cancer reported a worse outcome in patients with HPV-18-related tumors. [5][6][7][8] For other HPV types, the absence of detected HPV DNA sequences was reported to be associated with poor prognosis, 9 -11 whereas others found no relationship between HPV and outcome. [12][13][14][15][16][17] Most of these studies included patients who had received either surgery or a combination of surgery and radiotherapy.…”

mentioning

confidence: 99%

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Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer

Bachtiary

Obermair

Dreier

et al. 2002

To obtain information on the incidence and the clinical significance of infection with various types of the human papillomavirus (HPV) in cancer of the uterine cervix, we retrospectively examined the HPV status of 106 patients who had received radical radiotherapy for cervical cancer stages IB to IIIB. DNA was extracted from formalin-fixed, paraffinembedded biopsies and PCR was carried out to identify HPV types 16, 18, 31, 35, 33 and 45. To detect additional HPV types, consensus PCR products were cloned and sequenced. A catalyzed signal-amplified colorimetric in situ hybridization was carried out in 84 of 106 specimens as a positive control. Response to therapy, progression-free survival (PFS) and cervical cancer-specific survival (CCSS) were the statistical endpoints. Survival analysis was carried out using univariate and multivariate analysis (Cox regression). Ninety-six patients (90.6%) were HPV-positive and 42/96 (43.7%) were positive for multiple HPV types. Eight patients had persistent disease after radiotherapy. From these 8 patients, 7 were infected with multiple HPV types and only 1 patient had an infection with a single HPV type. After a median follow up period of 50 months, patients with multiple HPV infection had a significantly shorter PFS and CCSS compared to those with single HPV infection (24.8% and 34.9% vs. 64% and 60.8%, Log rank, p < 0.01 and 0.04). In multivariate analysis, the presence of multiple HPV types (RR 1.9), node status (RR 2.3), tumor size (RR 3.2) and histologic type (RR 4.8) were independent prognostic factors of CCSS. Our results demonstrate that the presence of multiple HPV types is associated with poor response and with reduced survival in cervical cancer patients who receive radiotherapy as the primary treatment.

“…Moreover, controversial data have been reported concerning the prognostic value of the HPV genotype associated with invasive carcinoma. A favourable outcome of tumours associated with HPV31 7 or HPV58 8 and an unfavourable outcome of tumours associated with HPV31 7,8 and a unfavourable outcome of tumours associated with HPV18 were reported, [9][10][11][12] whereas no significant association was observed in other studies. 13,14 In this context we have performed a virological and clinical retrospective study with a long-term follow up in order to (i) define the HPV types found in a large series of invasive carcinoma in France and (ii) assess the prognostic value of the different HPV types.…”

mentioning

confidence: 81%

Different outcome of invasive cervical cancer associated with high‐risk versus intermediate‐risk HPV genotype

Crémoux

Rochefordière

Savignoni

et al. 2008

Human papillomavirus (HPV) DNA sequences are associated with the large majority of invasive cervical carcinoma but the role of specific genotype(s) in the outcome of the disease is still debated. To determine the viral epidemiology in the French population of patients and the prognostic value of HPV genotypes in cervical cancer, we performed a retrospective study in 515 patients treated in our Institution from 1985 to 2005. Ninety-six percent of the cases were found associated with HPV DNA whereas 4% remained HPV negative. High-risk HPV 16/18 genotypes were found in 70% of the cases. HPV 18 was more frequently associated with adenocarcinoma (40.6%) than HPV 16 (10.4%) and found in tumours developed in younger women (mean age, 45.8 years) than HPV 16 (48.3 years) or other HPV types (53.6 years). In multivariate analysis, node involvement (p < 0.0001), parametria invasion (p 5 0.009), tumour size (p 5 0.01) and HPV status (p 5 0.02) were associated with disease-free survival (median follow-up 95 months). Disease outcome was better in tumours associated with intermediate risk HPV types (HPV 31,33,35,39, 52, 53, 58, 59, 73) than in tumours with high oncogenic types (HPV 16, 18, 45) (p 5 0.03). Node status and tumour size remained prognostic factor for overall survival. Our data show that HPV genotype is one of the biological factors associated with the outcome of cervical cancer. One third of invasive carcinoma were not associated with HPV 16/18, indicating that the screening for cervical neoplasia should be maintained after prophylactic vaccination against these HPV genotypes. ' 2008 Wiley-Liss, Inc.Key words: cervical cancer; HPV; prognosis Human papillomavirus (HPV) DNA sequences are associated with most of invasive cervical carcinoma worldwide 1 and the role of HPV as a causative agent of cervical neoplasia is well documented. 2 There is a large plurality of HPV types since more than 100 different genotypes have been identified 3 among which more than 40 infect ano-genital mucosa. Histological and virological analyses have shown that 3 groups of genital HPV could be identified according to their oncogenic properties. Low-risk HPVs (HPV6,11,42,43, 44. . .), present in low grade cervical intraepithelial neoplasia (CIN) but rare in invasive cancer, intermediaterisk HPVs (HPV 31,33,35, 51, 52, 58. . .), more prevalent in CIN than in invasive cancer, and high-risk HPVs (HPV16, 18, 45, 56. . .), more frequently found in invasive carcinoma than in CIN. 4 Experimental data have disclosed that high-risk E6 and E7 oncoprotein act in the tumour process by interfering with cell cycle G1-S checkpoint. 5 Virological epidemiology data show that HPV16 and HPV18 are the most prevalent genotypes found in invasive carcinoma worldwide but that there are significant geographic variations in the prevalence of less common genotypes. 6 In the perspective of prophylactic vaccination, it is thus necessary to accurately determine the prevalence of the different HPV types in cervical cancer at country level. Moreover, controversial data...