15 research outputs found
Cervical cancer studies on prevention and treatment
Cervical cancer is the fourth most common reason for cancer death amongst women worldwide, with 500 000 new cases every year. Most of these women live in developing countries. Cervical screening programs can reduce the incidence by 50%, but are not common in the developing world. In Sweden there are approximately 400 new cases of cervical cancer yearly, despite the existence of a screening program. Cervical cancer and dysplastic lesions in the cervix are caused by infection by the Human Papilloma Virus, mainly HPV 16 and 18. An alternative to cytological screening is screening for HPV DNA. The aim of this thesis was to analyze the screening history of women with cervical cancer, to find new techniques to screen women for cervical cancer, and to find out why some women do not attend screening. Furthermore, standard treatment for early cervical cancer is surgery including lymph node mapping, and patients have adverse effects from lymphadenectomies, so if a sentinel node procedure is accurate, it would be of value for the women. Of the population of cervical cancer patients diagnosed in the years 2009-2010, one third of the women were over 60 years of age, and one fourth were over 65. The women that followed the screening program had a better prognosis compared to women above the screening age (Hazard Ratio (HR) =5.3 95% CI 2.4-12.0, p<0.001). All the women whose cancer was identified via the screening program were alive at the median follow-up (36 months). This contrasted with the women that had symptoms, where 68 of 98 patients were alive at the median follow-up (p<0.0001).The vaginal self-sampling device that we validated showed good agreement with HPV analysis of liquid-based cytology (LBC) (kappa value 0.67 95% CI 0.53-0.81). When 1000 women who had not taken a cytology sample for over nine years were offered self-sampling at home, 15% responded. In contrast, when 500 women were offered flexible and free open clinic appointments, 4.2% came. The most common reason for non-attending was âuncomfortable with vaginal examinationâ. The sentinel node concept is safe when a sentinel node is identified on both sides, and the tumor is 2 cm or less. The negative predictive value was then 100%. The conclusions are that since so many women develop their cervical cancer after screening age, it would be advisable with an exit test. This exit test should ideally be an HPV test. In the case of hr-HPV positivity, the women could be offered a reflex cytology test. To reduce the non-attendance rate for cervical cancer screening, vaginal self-sampling for HPV-DNA is a possible method to use. Since so many women seem to be non-attendant due to being uncomfortable with vaginal examination, a self-test could be an attractive alternative. The final conclusion is that the sentinel node concept should be further investigated to make it possible to offer a sharp sentinel node for women with cervical cancer
Elderly women above screening age diagnosed with cervical cancer have a worse prognosis.
To analyze the cervical screening history in women with cervical cancer and their outcome
The sentinel node concept in early cervical cancer performs well in tumors smaller than 2 cm.
OBJECTIVE: The aim of the study was to evaluate the sentinel node (SLN) concept for lymphatic mapping in early stage cervical cancer. METHODS: 105 women with early stage (1a1-2a) cervical cancer were scheduled for the sentinel node procedure in conjunction with a complete pelvic lymphadenectomy. The day before surgery, 1-1.5 mL 120MBq Tc(99) albumin nanocolloid was injected submucosally at four points around the tumor followed by a lymphoscintigram (LSG) to achieve an overview of the radiotracer uptake. RESULTS: During surgery, the overall detection rate (gamma probe) of at least one SLN was 90% (94/105 women) whereas at least one SLN was identified in 94% (61/65 women) with a tumor 2 cm) node without radiotracer uptake. The negative predictive value for patients with cervical cancers </=2 cm was 100%. CONCLUSIONS: The SLN-technique seems to be an accurate method for identifying lymph node metastases in cervical cancer patients with tumors of 2 cm or smaller. In case of a unilateral SLN only, a complete lymphadenectomy should be performed on the radionegative side. All bulky nodes must be removed
HPV73
HPV73 is classified as possibly oncogenic and is not recognized by most commercial primary HPV screening platforms. The aim was to determine the prevalence of HPV73 among invasive cervical cancers, formalin-fixed paraffin embedded (FFPE) samples (N = 69), from southern Sweden during 2009 to 2010. Another aim was to determine proportions of HPV73 among Aptima HPV assay negative cervical cancers (N = 9, out of 206 cancers) and of high-grade cytological cervical diagnosis (N = 75, out of 5807 high grade lesions) in liquid-based cytology (LBC) samples collected between 2016 and 2019. We also investigated the distribution of HPV73 variants A1, A2 and B among HPV73-positive cases. HPV73 was detected by multiplex MGP-PCR and Luminex, and HPV73 variants were identified by sequencing PCR amplicons. HPV73 was detected in 2.9% (2/69, 95% CI: 0.18-9.9) of the FFPE cervical cancer series. Among the Aptima HPV-negative LBC samples, HPV73 was present in 55.5% (5/9) of the cancers and 29.3% (22/75) of the different grades of cervical diagnosis. The A1, A2 and B variants were present in 6.9% (2/29), 82.7% (24/29) and 10.3% (3/29) of the HPV73-positive women, respectively. Among the seven HPV73 cancer cases (two FFPE samples and five LBC samples), six A2 and one A1 isolate were detected. In summary, the A2 variant of HPV73 was most common in our region. In addition, the observed prevalence of HPV73 (2.9%) in cervical cancers and its relative high occurrence (55.5%) among Aptima HPV-negative cancers urge that detection of HPV73 should be included in future primary HPV screening programs
HPV73 in cervical cancer and distribution of HPV73 variants in cervical dysplasia
HPV73 is classified as possibly oncogenic and is not recognized by most commercial primary HPV screening platforms. The aim was to determine the prevalence of HPV73 among invasive cervical cancers, formalin-fixed paraffin embedded (FFPE) samples (N = 69), from southern Sweden during 2009 to 2010. Another aim was to determine proportions of HPV73 among Aptima HPV assay negative cervical cancers (N = 9, out of 206 cancers) and of high-grade cytological cervical diagnosis (N = 75, out of 5807 high grade lesions) in liquid-based cytology (LBC) samples collected between 2016 and 2019. We also investigated the distribution of HPV73 variants A1, A2 and B among HPV73-positive cases. HPV73 was detected by multiplex MGP-PCR and Luminex, and HPV73 variants were identified by sequencing PCR amplicons. HPV73 was detected in 2.9% (2/69, 95% CI: 0.18-9.9) of the FFPE cervical cancer series. Among the Aptima HPV-negative LBC samples, HPV73 was present in 55.5% (5/9) of the cancers and 29.3% (22/75) of the different grades of cervical diagnosis. The A1, A2 and B variants were present in 6.9% (2/29), 82.7% (24/29) and 10.3% (3/29) of the HPV73-positive women, respectively. Among the seven HPV73 cancer cases (two FFPE samples and five LBC samples), six A2 and one A1 isolate were detected. In summary, the A2 variant of HPV73 was most common in our region. In addition, the observed prevalence of HPV73 (2.9%) in cervical cancers and its relative high occurrence (55.5%) among Aptima HPV-negative cancers urge that detection of HPV73 should be included in future primary HPV screening programs
Vaginal self-sampling without preservative for human papillomavirus testing shows good sensitivity.
BACKGROUND: Several strategies have been used to reach non-attending women in organized cervical-cancer-screening programs, with varying success. Self-sampling (SS) for HPV is effective for increasing coverage in screening programs, but requires expensive commercial sampling kits. OBJECTIVE: We aimed to evaluate if vaginal SS, without commercial preservatives was adequate for HPV testing. STUDY DESIGN: Women with abnormal cervical smears as determined from the organized screening program were invited to a colposcopy clinic. The 121 women were asked to insert a cotton swab into the vagina and rotate it, put the cotton swab into a sterile cryotube, break the upper part of the stick and put the cap on. Thereafter, the gynaecologist collected a liquid based cytology (LBC) sample. The presence of HPV-types in SS and LBC samples was analysed with PCR and luminex-based typing. RESULTS: High-risk-HPV (hr-HPV) DNA was found in 65 of the tested 108 SS (60%; 95% CI 0.50-0.69), whereas LBC found hr-HPV in 64/108 samples (59%; 95% CI 0.49-0.69). The agreement between sampling with SS and LBC was good, kappa value 0.67 (95% CI; 0.53-0.81). The sensitivity for SS with hr-HPV to find HSIL was 81% (95% CI; 67-95%), specificity 49% (95% CI; 37-60%) and the sensitivity for LBC with hr-HPV to find HSIL was 90% (95% CI 80-100%), specificity53% (95% CI; 42-65%). CONCLUSIONS: This new vaginal self-sampling method detects hr-HPV-infections with similar sensitivity as a cervical smear taken by a gynaecologist. This self-sampling method is cost-effective and well tolerated, and the kit is suitable for regular mail transport
Follow up with HPV test and cytology as test of cure, 6 months after conization, is reliable
Introduction: Human papillomavirus (HPV) infection is an objective marker with a high sensitivity for finding cervical dysplasia. The objective of the current study is to investigate whether HPV testing, combined with liquid-based cytology, is reliable as a test of cure after the loop electrical excision procedure (LEEP). Material and methods: The LEEP was performed in 330 women for excision of cervical dysplasia. Follow up consisted of HPV testing and liquid-based cytology at six, 12, and 36 months after treatment. Patients with negative co-testing after 6 months were re-examined after 3 years. Patients who tested positive for high-risk HPV and/or dysplasia were followed up 12 months postoperatively. Results: At 6 months, the co-testing was double negative in 169 of 260 tested cases (65%). A positive high-risk HPV test (n = 40) was associated with cytological abnormalities (p < 0.001). After 3 years, 227 of 275 examined cases (83%) co-tested negative, including 154 patients who had already tested negative at 6 months and 37 cases with viral clearance at 12 months. Of 26 patients with high-risk HPV at the 3-year follow up, six had LSIL findings on liquid-based cytology, but neither HSIL lesions nor glandular atypia or cervical cancer was found. A negative high-risk HPV test showed a negative predictive value for HSIL of 100% (95% CI 99.8â100%). Conclusions: Negative co-testing 6 months after LEEP can be considered a reliable test of cure as 3-year follow-up results are consistent with neither HSIL or cancer
Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities.
Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology
Vaginal and urine self-sampling compared to cervical sampling for HPV-testing with the cobas 4800 HPV test
Background/Aim: To compare human papillomavirus (HPV) DNA detection in self-collected vaginal and urine samples with clinician-taken cervical samples in relation to histology. Materials and Methods: Self-collected vaginal, urine and clinician-taken cervical samples were analyzed from 218 women with the Cobas 4800 HPV test (Roche Molecular Diagnostics). Results: The sensitivity for detection of HPV in the vaginal self-sampling test was 96.4% and in urine was 83.9% relative to detection by clinician-taken cervical sample. The vaginal self-sampling and the clinician-taken HPV tests had the same sensitivity of 92.8% (95% confidence interval=86.3-96.8%) and specificity for detection of high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS). Detection in urine samples had a sensitivity of 76.3% (95% confidence interval=67.9-84.2%) for HSIL/AIS. Conclusion: The Cobas 4800 HPV test detects high-grade pre-cancerous cervical lesions in self-collected vaginal samples with the same high sensitivity as in clinician-taken cervical samples
Comparison of use of vaginal HPV self-sampling and offering flexible appointments as strategies to reach long-term non-attending women in organized cervical screening.
Many cervical cancers occur among women who have not attended cervical screening. Strategies to reach non-attending women may improve the effectiveness of cervical screening programmes