Clinical Effect of Human Papillomavirus Genotypes in Patients With Cervical Cancer Undergoing Primary Radiotherapy

Wang, Chun‐Chieh; Lai, Chyong‐Huey; Huang, Hsuan-Rong; Chao, Angel; Chang, Chee‐Jen; Chang, Ting‐Chang; Chou, Hung-Hsueh; Hong, Ji-Hong

doi:10.1016/j.ijrobp.2009.09.021

Cited by 49 publications

(57 citation statements)

References 40 publications

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“…This fig. is higher than previously reported (20,21). Kusanagi et al reported that HPV has been rarely detected in some types of adenocarcinoma of the uterus cervix (31).…”

Section: Discussionmentioning

confidence: 70%

“…By contrast, HPV species had no impact on LC or OS rates in patients with uterine CC. These findings contrast with those of Wang et al who found a significant effect of HPV species on LC and local progression-free survival rates, respectively (20). Meanwhile, Hall et al assessed that the HPV α-9 and α-7 species had similar radiosensitivity by performing assays in clonal CC cell lines (21).…”

Section: Discussionmentioning

confidence: 80%

“…Two HPV species, α-7 (HPV 18, 39, 45, 59, and 68) and α-9 (HPV 16, 31, 33, 35, 52, and 58), account for >80% of all CCs (19). Wang et al reported that patients with HPV α-7-positive CC had worse local control (LC) after RT compared with HPV α-9-positive patients (20). However, by performing assays in clonal CC cell lines, Hall et al revealed that poor prognosis associated with HPV species might not be explained by intrinsic radiosensitivities because cells harboring the HPV α-9 and α-7 species had similar radiosensitivities (21).…”

Section: Introductionmentioning

confidence: 99%

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Human papillomavirus genotype affects metastatic rate following radiotherapy in patients with uterine cervical cancer

et al. 2017

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Abstract. Human papillomavirus (HPV) infection is well known as a major etiological risk factor associated with carcinogenesis in uterine cervical cancer. However, few reports have investigated the association between HPV genotype and outcome in patients with uterine cervical cancer following radiotherapy (RT). The aim of the present study was to investigate the association between the HPV genotype and clinical outcome following RT in Japanese patients with uterine cervical cancer. Between November 2001 and August 2006, 157 Japanese women with uterine cervical cancer were treated with RT or concurrent chemoradiotherapy with curative intent. Pretreatment, formalin-fixed, paraffin-embedded biopsies were obtained from 83 patients. HPV genotypes were determined using the polymerase chain reaction method. Patients were categorized, according to HPV L1 protein sequence homology, into the HPV α-9 (HPV 16,31,33, 52, and 58),39, 45, 59, and 68) or 'other' (HPV 51 and 56) groups. Associations between HPV genotype and clinical outcome following RT were evaluated. A total of 54 (65.1%) tumors were HPV α-9-positive, 13 (15.7%) were HPV α-7-positive, 2 (2.4%) were categorized under 'other' and 14 (16.9%) were HPV-negative. There were no significant differences in age, FIGO stage, regional lymph node metastases rate at diagnosis, or concurrent chemotherapy administration between the HPV α-9 and α-7 groups. The median follow-up period was 52 months (range, 2-156 months). The 5-year disease-free survival rates were 54.5 and 30.8% in the HPV α-9 and α-7 groups, respectively (P=0.034), and the 5-year distant metastasis rates were 38.0 and 69.2%, respectively (P=0.015). There were no significant differences in the 5-year local control or overall survival (OS) rates between the two groups. HPV genotype affected the 5-year distant metastatic rate, however not the 5-year local control or OS rate in patients with uterine cervical cancer following RT. IntroductionUterine cervical cancer (CC) is the second most common cancer among women, worldwide (1). The annual global incidence of CC in 2012 was 528,000 cases, and the annual global mortality rate was 266,000 deaths, with 85% of cases occurring in developing countries, where CC is a leading cause of cancer-related death in women (2). Oncogenic type human papillomavirus (HPV) infection is a major etiologic risk factor (3) associated with carcinogenesis (4). More than 100 HPV types have been identified, with a subset of these being classified as high risk. HPV 16 and HPV 18 are the most commonly detected genotypes occurring in 71% of invasive CCs (5). Current detection methods have uncovered a HPV prevalence of 95-100% in women with CC (6,7).The primary treatment strategy for uterine CC consists of surgery or radiotherapy (RT). Surgery is typically reserved for early-stage disease and small lesions including stage IA, IB1, and selected IIA1 diseases (8). Based on the results of randomized clinical trials, concurrent chemoradiotherapy (CCRT) has become the primary treatment for stage IB2...

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“…This fig. is higher than previously reported (20,21). Kusanagi et al reported that HPV has been rarely detected in some types of adenocarcinoma of the uterus cervix (31).…”

Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human papillomavirus genotype affects metastatic rate following radiotherapy in patients with uterine cervical cancer

et al. 2017

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“…In this study of 1,010 patients undergoing primary radiotherapy for ICC, Wang et al (2010) determined three HPV associated "risk groups" ("high-risk," "medium risk" and "low risk) that were independent of other prognostic variables (age, FIGO, stage, metastasis). 10 The high risk group were those in which HPV infection was either not detected or those infected with a species Group 7 type (which includes HPV 18). Although we did not see a similar association with HPV 18, these data reconcile with our finding that a status of "HPV not detected" was associated with the lowest survival time (25% mortality time of 554 days).…”

Section: Short Reportmentioning

confidence: 99%

“…Furthermore, existing studies that address the impact of type on survival are heterogeneous, specifically with respect to assay choice (serological vs. molecular), the method of case selection (i.e., whether the cervix was the primary tumor) and whether cervical cancer was confirmed as the primary cause of death (or not). [5][6][7][8][9][10][11] In addition, many studies are derived from small sample sets (<50) of patients undergoing specific treatments.Gaining a more comprehensive insight into how HPV type affects survival is important, particularly as we expect that the incidence of HPV 16 and 18 associated ICC will …”

mentioning

confidence: 99%

Influence of HPV type on prognosis in patients diagnosed with invasive cervical cancer

Cuschieri

Brewster

Graham

et al. 2014

Intl Journal of Cancer

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While much is known about the influence of HPV type on the progression of pre-invasive cervical lesions, the impact of HPV type on cervical cancer prognosis is less evidenced. Thus, we assessed the impact of HPV type on the survival of women diagnosed with cervical cancer. A total of 370 cases of cervical cancer were assessed. Univariate analysis is presented using Kaplan-Meier survival curves and log-rank statistics and multivariable Cox proportional hazard models were generated using age group, socio-economic deprivation, FIGO stage, differentiation and HPV type. HPV grouping was considered in a number of ways with particular reference to the presence or absence of HPV 16 and/or 18. In the univariate analysis, FIGO, age at diagnosis and treatment were associated with poorer survival (p < 0.0001) as was absence of HPV 16 and/or 18 (p 5 0.0460). The 25% mortality time in the non-HPV 16/18 vs. HPV16/18 positive group was 615 days and 1,307 days respectively. An unadjusted Cox PH model based HPV16/18 vs. no HPV 16/18 resulted in a hazard ratio of 0.669 (0.450, 0.995). Adjusting for deprivation, FIGO and age group resulted in a hazard ratio of 0.609 (0.395, 0.941) p 5 0.025. These data indicate that cancers associated with HPV 16 and/or 18 do not confer worse survival compared to cancers associated with other types, and may indicate improved survival. Consequently, although HPV vaccine is likely to reduce the incidence of cervical cancer it may not indirectly improve cervical cancer survival by reducing the burden of those cancers caused by HPV16/18.It is now well established that the majority of invasive cervical cancers (ICCs) are associated with HPV 16 and or 18; in a global meta-analysis of nearly 31,000 cases these two types were responsible for between 70 and 76% of ICC in nearly all countries assessed.1 There is also significant evidence to suggest that HPV 16 and 18 confer a worse prognosis in the context of cervical infection and pre-invasive disease. In the influential study of Khan et al. (2005), the authors found the 10 year cumulative incidence of high-grade cervical lesions (CIN31) in around 20,000 women with normal or low grade cervical smears was 17.2% in HPV 16 positive women, 13.6% in HPV 18 positive women and only 3.0% in women positive for other high risk (HR) HPV types. 2The observation that HPV 16 is the highest-risk of the high risk types has been shown to be consistent in colposcopy populations-and consequently, clinical management algorithms that incorporate HPV genotyping for risk stratification are being developed, as are high-throughput HPV consensus assays that include separate channels for HPV 16 and 18. 3,4 However, although there is now much evidence on the impact of HPV type in the trajectory of pre-invasive disease, there is little information on how it affects prognosis in ICC. Furthermore, existing studies that address the impact of type on survival are heterogeneous, specifically with respect to assay choice (serological vs. molecular), the method of case selection (i.e., whe...

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Radiation sensitivity assay with a panel of patient‐derived spheroids of small cell carcinoma of the cervix

Nakajima

Endo

Okuyama

et al. 2014

Intl Journal of Cancer

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Small cell carcinoma of the uterine cervix (SCCC) is a rare cancer with a poor prognosis for which no standard treatment exists. Here, we successfully established panels of patient-derived spheroid cultures from six SCCC patient samples by cancer tissue-originated spheroids (CTOS) method. To assess the intrinsic radiosensitivity and mechanism of radioresistance in individual SCCC patients, we further developed an in vitro sensitivity assay for radiation. Radiation sensitivity in the CTOS assay varied among individual cases and was consistent with in vivo radiation sensitivity using CTOS-derived xenograft tumors in the examined cases. Furthermore, by comparing gene expression in CTOSs with different radiosensitivity, we found that expression of hypoxia-inducible factor-1a (HIF-1a) target genes was upregulated in resistant CTOSs. HIF-1a protein levels increased several hours after irradiation. In a radioresistant CTOS, an inhibitor of heat shock protein 90 (HSP90) suppressed radiation-induced HIF-1a expression. Suppression of HIF-1a by small hairpin RNA significantly enhanced the effect of radiation, at least in part by promoting radiation-induced apoptosis. HSP90 inhibitor also increased radiation sensitivity. Our results indicate that radiation-induced HIF-1a upregulation was one mechanism of radioresistance in a radioresistant SCCC CTOS. Accumulating CTOS lines may provide a good platform to study characters of rare cancers like SCCC.

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Clinical Effect of Human Papillomavirus Genotypes in Patients With Cervical Cancer Undergoing Primary Radiotherapy

Cited by 49 publications

References 40 publications

Human papillomavirus genotype affects metastatic rate following radiotherapy in patients with uterine cervical cancer

Human papillomavirus genotype affects metastatic rate following radiotherapy in patients with uterine cervical cancer

Influence of HPV type on prognosis in patients diagnosed with invasive cervical cancer

Radiation sensitivity assay with a panel of patient‐derived spheroids of small cell carcinoma of the cervix

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