Low Initial Human Papilloma Viral Load Implicates Worse Prognosis in Patients With Uterine Cervical Cancer Treated With Radiotherapy

Kim, Joo-Young; Park, Sohee; Nam, Byung–Ho; Roh, Ju-Won; Lee, Chae Hyeong; Kim, Chongam; Shin, Hyung Shik; Lee, Su-Kyoung; Kong, Sun‐Young; Seong, Moon Woo; Han, Tae-Jin; Lee, Me-Yeon; Cho, Kwan Ho; Park, Soo‐Jin

doi:10.1200/jco.2009.22.4659

Cited by 56 publications

(60 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Against this background, however, Kim et al reported that semi-quantitatively measured HPV DNA-load was a strong independent prognostic factor for disease-free survival of patients with cervical cancer treated with radical RT. 14 Thus, we aimed to analyze the impact of HPV16 DNA load on treatment outcomes in our series of anal SCC patients treated with standard CRT. In agreement with the findings by Kim et al, we showed that high HPV16 DNA load is an independent prognostic factor associated with improved locoregional tumor control and overall survival.…”

Section: Cancer Cell Biologymentioning

confidence: 99%

mentioning

confidence: 99%

“…In patients with cervical cancer, Kim et al recently reported that the semi-quantitatively measured HPV DNA load was a strong independent prognostic factor for diseasefree survival after radical RT. 14 The recent understanding of HPV infection as a causative factor in tumorigenesis, treatment response and prognosis further encouraged investigations on surrogate biomarkers for HPV infection. Amongst these factors, the cell cycle regulatory protein p16 INK4a (also named CDKN2A) has emerged as the best validated candidate due to its association with high-risk HPV infection.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Human papillomavirus DNA load and p16^INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

et al. 2014

View full text Add to dashboard Cite

As the detection rate of HPV-DNA in anal carcinoma commonly exceeds 90%, a comparison between sole HPV-positive and HPV-negative cancers with respect to treatment response following chemoradiotherapy (CRT) and long-term oncological outcome is challenging. Against this background, we aimed to assess HPV types and HPV DNA load in formalin-fixed paraffinembedded tissue (FFPE) of 95 patients treated with standard CRT for anal cancer to correlate viral load ( /> median) with local failure, distant metastases, cancer-specific (CSS) and overall survival (OS) rates. Various clinicopathologic parameters and the immunohistochemical marker p16 INK4a were evaluated for any correlation with HPV16 DNA load and were included in uni-and multivariate analyses. The overall prevalence of HPV DNA was 95.8% with HPV16 monoinfection being the most commonly encountered HPV type (78.9%), followed by HPV16 and 31,35,39,44, 58, 66 and 81 dual infection in 9 patients (9.5%). HPV16 DNA load was significantly associated with p16 INK4a expression (p 5 0.001). Patients with HPV16 DNA load median and low p16 INK4a expression showed significantly worse local control (HPV16 DNA load: univariate p 5 0.023, multivariate p 5 0.042; p16 INK4a : univariate p 5 0.021), and OS (HPV16 DNA load: univariate p 5 0.02, multivariate p 5 0.03). Moreover, a combined HPV16 DNA load and p16 INK4a variable revealed a significant correlation to decreased local failure, and increased CSS and OS (p 5 0.019, p 5 0.04 and p 5 0.031). In conclusion, these data indicate that HPV16 DNA load and p16 INK4a expression are significant prognostic factors for local tumor control and overall survival of patients with anal SCC following CRT.The majority of anal squamous cell carcinoma (SCC) is considered to originate from infection with human papilloma viruses (HPV). 1,2 Especially the role of high-risk oncogenic HPV types, most prominently HPV type 16 (HPV16), in the etiology of anal SCC is well established by a multitude of epidemiological and experimental investigations. 3,4 As a consequence, technologies for the detection of HPV DNA may constitute valuable screening tools for anal malignancies and are of important clinical relevance, especially after the development of a preventive vaccine for both men and women. 5 Depending on the method used, the prevalence of HPV DNA in anal carcinoma ranges from 75% to 100% with HPV16 (>75%) and less frequent HPV18 (<10%) detection in the majority of cases. 6,7 In clinical series of head and neck as well as cervical SCC, recent data indicate that treatment response to radiotherapy (RT) or chemoradiotherapy (CRT) is superior in HPV-positive tumors as compared with their HPV-negative counterparts. [8][9][10] An increased sensitivity of HPV-positive tumor cells towards irradiation and chemotherapeutic agents was also observed in vitro and in animal studies. [11][12][13] However, as the detection rate of HPV DNA in anal SCC commonly exceeds 90%, a comparison between sole HPV-positive and HPV-negative cancers with respect to treatment respon...

show abstract

Section: Cancer Cell Biologymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Human papillomavirus DNA load and p16^INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In nasal NK/Tcell lymphoma, a low viral load of Epstein-Barr virus detected in formalin-fixed paraffin-embedded tissue was reported to be associated with better overall survival of the patients, compared to the high viral load (Hsieh et al, 2007). The prognostic value of HPV viral load has been evaluated in studies on HPV-associated cancers such as tonsillar squamous cell carcinoma and cervical carcinoma (Mellin et al, 2002;Datta et al, 2006;de Boer et al, 2007;Cohen et al, 2008;Kim et al, 2008Kim et al, : 2009Gnanamony et al, 2009;Kang et al, 2011). The studies on HPV16 DNA viral load detected in tissue samples (fresh frozen or paraffin-embedded) of tonsillar carcinoma demonstrated a significant association between low viral load and adverse prognosis (Mellin et al, 2002;Cohen et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…The clinical significance Sumalee Siriaunkgul 1 , Utaiwan Utaipat 2 , Supaporn Suwiwat 3 , Jongkolnee Settakorn 1 , Kornkanok Sukpan 1 , Jatupol Srisomboon 4 , Surapan Khunamornpong 1 * of HPV viral load in patients with cervical carcinoma has been evaluated in only a small number of studies (Datta et al, 2006;De Boer et al, 2007;Kim et al, 2008Kim et al, : 2009Gnanamony et al, 2009;Kang et al, 2011). An association between a high HPV viral load in cervical carcinoma and a better prognosis has been described (Datta et al, 2006;Kim et al, 2009). To our knowledge, a study on HPV viral load in cervical NECA has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of HPV18 DNA Viral Load in Patients with Early-Stage Neuroendocrine Carcinoma of the Uterine Cervix

Siriaunkgul

Utaipat²,

Suwiwat³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffinembedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load ≤5.00 copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients.

show abstract

HPV status and HPV16 viral load in anal cancer and its association with clinical outcome

et al. 2022

View full text Add to dashboard Cite

Background:The incidence of anal cancer is increasing globally. Evidence-based improvement in early detection and management of this morbid cancer is thus required. In other cancers associated with Human Papillomavirus (HPV), viral status and dynamics, including viral load (VL) has been shown to influence clinical outcome. Our aim was to determine the influence of HPV status and HPV16 VL on the clinical outcomes of anal cancer patients.Methods: A total of 185 anal cancer lesions were genotyped for HPV. Of the HPV16 positive component, VL was determined using a digital droplet PCR assay.The association of qualitative HPV status and VL (low (<12.3), medium (12.3-57) and high (>57 copies/cell)) on overall survival and hazard of death was assessed.Results: Of the 185 cases, 164 (88.6%) samples were HPV positive. HPV16 was detected in 154/185 samples (83.2%). HPV positive status was associated with improved overall survival in the univariate analysis [hazard ratio (HR) of 0.44, 0.23-0.82, p = 0.01]. When adjusted by age, sex, stage and response to treatment, the association of positive HPV status with improved survival remained (HR 0.24 [0.11-0.55] p < 0.001). High VL was associated with improved overall survival in the univariate analysis with a HR of 0.28 (0.11-0.71, p = 0.007). When adjusted only by age and sex, high VL was associated with better overall survival (HR 0.27, 0.11-0.68 p = 0.006).Conclusions: HPV status appears to be independently associated with improved outcomes in anal cancer patients. Moreover, HPV viral load quantification may be informative for further risk stratification and warrants further investigation.

show abstract

Low Initial Human Papilloma Viral Load Implicates Worse Prognosis in Patients With Uterine Cervical Cancer Treated With Radiotherapy

Abstract: Our data suggest that HPV viral load is a strong independent prognostic factor for DFS. HPV type 18 showed a significant relationship with poor radiotherapy outcome in univariate analysis, but not in multivariate analysis.

Cited by 56 publications

References 17 publications

Human papillomavirus DNA load and p16^INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

Human papillomavirus DNA load and p16^INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

Prognostic Value of HPV18 DNA Viral Load in Patients with Early-Stage Neuroendocrine Carcinoma of the Uterine Cervix

HPV status and HPV16 viral load in anal cancer and its association with clinical outcome

Contact Info

Product

Resources

About

Low Initial Human Papilloma Viral Load Implicates Worse Prognosis in Patients With Uterine Cervical Cancer Treated With Radiotherapy

Abstract: Our data suggest that HPV viral load is a strong independent prognostic factor for DFS. HPV type 18 showed a significant relationship with poor radiotherapy outcome in univariate analysis, but not in multivariate analysis.

Cited by 56 publications

References 17 publications

Human papillomavirus DNA load and p16INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

Human papillomavirus DNA load and p16INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

Prognostic Value of HPV18 DNA Viral Load in Patients with Early-Stage Neuroendocrine Carcinoma of the Uterine Cervix

HPV status and HPV16 viral load in anal cancer and its association with clinical outcome

Contact Info

Product

Resources

About

Human papillomavirus DNA load and p16^INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

Human papillomavirus DNA load and p16^INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy