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| 2. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 3. |
- Frisch, Morten, et al.
(författare)
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Sexually transmitted infection as a cause of anal cancer
- 1997
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 337:19, s. 1350-1358
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The incidence of anal cancer has increased in recent decades, particularly among women. To identify underlying risk factors, we conducted a population-based case-control study in Denmark and Sweden. METHODS: We conducted telephone interviews with 324 women and 93 men in whom invasive or in situ anal cancer was diagnosed between 1991 and 1994, 534 controls with adenocarcinoma of the rectum, and 554 population controls. The interviews covered a wide spectrum of possible risk factors for anal cancer. Odds ratios were calculated by logistic regression. Specimens of anal-cancer tissue and samples of rectal adenocarcinomas were tested for human papillomavirus (HPV) DNA with the polymerase chain reaction. RESULTS: Multivariate analysis revealed consistent and statistically significant associations between measures of sexual promiscuity and the risk of anal cancer in both men and women. There was a significant trend toward an association between higher numbers of partners of the opposite sex in women (P<0.001) and men (P<0.05) and strong associations with a variety of venereal diseases. In women, receptive anal intercourse, particularly before the age of 30 years, and venereal infections in the partner were also associated with an increased risk (odds ratios, 3.4 and 2.4, respectively). Fifteen percent of the men with anal cancer reported having had homosexual contact, as compared with none of the controls (P<0.001). High-risk types of HPV, notably HPV-16, were detected in 84 percent of the anal-cancer specimens examined, whereas all rectal-adenocarcinoma specimens tested were negative for HPV. CONCLUSIONS: Our study provides strong evidence that a sexually transmitted infection causes anal cancer. The presence of high-risk types of HPV, notably HPV-16 (which is known to cause cancer of the cervix), in the majority of anal-cancer tissue specimens suggests that most anal cancers are potentially preventable.
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| 4. |
- Frisch, Morten, et al.
(författare)
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Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses
- 1999
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 59:3, s. 753-757
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Tidskriftsartikel (refereegranskat)abstract
- High-risk types of human papillomaviruses (hrHPVs) may be a necessary cause in cervical cancer and in some subtype of anal, vulvar, and penile cancers. Large studies aimed at characterizing hrHPV-associated and non-hrHPV-associated subtypes of anal carcinomas are, however, lacking. We searched for human papillomavirus type 16 and 13 other hrHPVs in tumor tissue by PCR and performed a systematic histological evaluation of specimens from 386 patients with anal cancer (86% invasive; 302 women and 84 men). Cancers in women and homosexual men were more often hrHPV positive (P < 0.01) and located in the anal canal (P < or = 0.01) than were cancers in heterosexual men. In both women and men, anal canal cancers contained hrHPV clearly more often than did perianal skin cancers, and increasing hrHPV positivity was seen with higher localization in the anal canal. Indeed, 95 and 83% of cancers involving the anal canal in women and men, respectively, were hrHPV positive versus 80 and 28% of perianal skin cancers (P-trend < 0.001). Basaloid feature, adjacent anal intraepithelial neoplasia, poor or absent keratinization, and a predominance of small or medium neoplastic cells were all strongly positively associated with hrHPV status. Like cancer of the uterine cervix, the development of cancer of the anal canal may require infection with hrHPV, whereas a dual etiology of perianal skin cancers bears parallels to vulvar and penile cancers.
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| 5. |
- Meijer, Chris J. L. M., et al.
(författare)
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Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:3, s. 516-520
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Tidskriftsartikel (refereegranskat)abstract
- Given the strong etiologic link between high-risk HPV infection and cervical cancer high-risk HPV testing is now being considered as an alternative for cytology-based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high-risk HPV is not inherently useful unless it is informative for the presence of high-grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high-risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high-grade CIN and cervical cancer to minimize redundant or excessive follow-up procedures for high-risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high-risk HPV testing by hybrid capture 2 and GP5+/6+-PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high-risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for high-risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays. (C) 2008 Wiley-Liss, Inc.
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| 6. |
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| 7. |
- Forslund, Ola, et al.
(författare)
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Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish Women.
- 2002
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Ingår i: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 66:4, s. 535-541
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5(+)/6(+)) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.
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| 8. |
- Arbyn, Marc, et al.
(författare)
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Clinical applications of HPV testing: A summary of meta-analyses
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:Suppl. 3, s. 78-89
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Tidskriftsartikel (refereegranskat)abstract
- Background: More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. Material and methods: A summary is given from recently published meta-analyses on three possible clinical applications of human papillomavirus (HPV)-DNA testing: triage of women with equivocal or low-grade cytological abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Results: Consistent evidence is available indicating that HPV-triage with the Hybrid Capture-2 assay (HC2) is more accurate (significantly higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. When triaging women with low-grade squamous intraepithelial lesions (LSIL), a reflex HC2 test does not show a significantly higher sensitivity, but a significantly lower specificity compared to a repeat Pap smear. After treatment of cervical lesions, HPV testing easily detects (with higher sensitivity and not lower specificity) residual or recur-rent CIN than follow-up cytology. Primary screening with HC2 generally detects 23% (95% confidence interval, CI: 13-23%) more CIN-2, CIN-3, or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASCUS) or LSIL, but is 6% (95% CI: 4-8%) less specific. By combined HPV and cytology screening, a further 4% (95% CI: 3-5%) more CIN-3 lesions can be identified but at the expense of a 7% (95% CI: 5-9%) loss in specificity, in comparison with isolated HC2 screening. Conclusions: Sufficient evidence exists to recommend HPV testing in triage of women with atypical cytology and in surveillance after treatment of CIN lesions. In the United States, recently reviewed knowledge has resulted in the approval of combined cytology and HC2 primary screening in women older than 30 years. However, in Europe, cytology-based screening still remains the standard screening method. The European screening policy will be reviewed based on the longitudinal results of randomised population trials which are currently underway. (c) 2006 Elsevier Ltd. All rights reserved.
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| 9. |
- Cuzick, Jack, et al.
(författare)
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Overview of Human Papillomavirus-Based and Other Novel Options for Cervical Cancer Screening in Developed and Developing Countries
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Screening for cervical cancer precursors by cytology has been very successful in countries where adequate resources exist to ensure high quality and good coverage of the population at risk. Mortality reductions in excess of 50% have been achieved in many developed countries; however the procedure is generally inefficient and unworkable in many parts of the world where the appropriate infrastructure is not achievable. A summary and update of recently published meta-analyses and systematic reviews on four possible clinical applications of human papillomavirus (HPV) DNA testing is provided in this article: (1) triage of women with equivocal or low-grade cytological abnormalities; (2) follow-up of women with abnormal screening results who are negative at colposcopy/biopsy; (3) prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN), and most importantly (4) primary screening HPV DNA test, solely or in combination with Pap smear to detect cervical cancer precursors. There are clear benefits for the use of HPV DNA testing in the triage of equivocal smears, low-grade smears in older women and in the post-treatment surveillance of women after treatment for CIN. However, there are still issues regarding how best to use HPV DNA testing in primary screening. Primary screening with Hybrid Capture (R) 2 (HC2) generally detects more than 90% of all CIN2, CIN3 or cancer cases, and is 25% (95% CI): 15-36%) relatively more sensitive than cytology at a cut-off of abnormal squamous cells of undetermined significance (ASCUS) (or low-grade squamous intraepithelial lesions (LSIL) if ASC-US unavailable), but is 6% (95% CI: 4-7%) relatively less specific. Several approaches are currently under evaluation to deal with the lower specificity of HPV DNA testing as associated with transient infection. These include HPV typing for HPV-16 and -18/45, markers of proliferative lesions such as p16 and mRNA coding for the viral E6 and/or E7 proteins, with a potential clinical use recommending more aggressive management in those who are positive. In countries where cytology is of good quality, the most attractive option for primary screening is to use HPV DNA testing as the sole screening modality with cytology reserved for triage of HPV-positive women. Established cytology-based programmes should also be gradually moving towards a greater use of HPV DNA testing to improve their efficacy and safely lengthen the screening interval. The greater sensitivity of HPV DNA testing compared to cytology argues strongly for using HPV DNA testing as the primary screening test in newly implemented programmes, except where resources are extremely limited and only programmes based on visual inspection are affordable. In such countries, use of a simple HPV DNA test followed by immediate 'screen and treat' algorithms based on visual inspection in those who are HPV-positive are needed to minimise the number of visits and make best use of limited resources. A review of studies for visual inspection methods is presented. The fact that HPV is a sexually transmitted infection may lead to anxiety and concerns about sexual relationships. These psychosocial aspects and the need for more information and educational programmes about HPV are also discussed in this article. (C) 2008 Elsevier Ltd. All rights reserved.
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