Guía de cribado del cáncer de cuello de útero en España, 2014 / No disponible

No disponible

Guía de cribado del cáncer de cuello de útero en España, 2014 / No disponible

No disponible

Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study.

BACKGROUND: Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing. METHODS: A total of 27,349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined. RESULTS: The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001). CONCLUSIONS: The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.

Epidemiology and costs of screening and management of precancerous lesions of the cervix in Spain.

OBJECTIVE: Oncogenic human papillomaviruses (HPVs) are essential causes of cervical cancer. Screening prevents cancer by detecting precancerous lesions (cervical intraepithelial neoplasia, CIN). Our aim was to assess the annual number of Pap smears and CIN diagnoses in Spain and to estimate associated management costs. MATERIALS AND METHODS: A 1-year retrospective cross-sectional study was conducted among 65 gynecologists from public primary health care centers in 6 autonomous regions in Spain. We documented the total number of Pap smears performed and the management of women with CIN. Data on health care resource use related to CIN management for 2 years after diagnosis were collected and combined with unit costs to assess the mean cost per patient. We extrapolated to the general female Spanish population to estimate the total cost of screening and CIN management from the third-party payer's perspective. RESULTS: In our study sample, 3.5% of routine Pap smears were abnormal. We estimated that 7.6 million Pap smears are performed annually in Spain, at a cost of 622 million euro (US$987). Furthermore, 40,530 women are annually diagnosed with CIN 1, 26,243 with CIN 2, and 28,423 with CIN 3. The mean cost of CIN management per patient was 1,115 euro for CIN 1, 1,626 euro for CIN 2, and 2,090 euro for CIN 3. The total cost of CIN management was estimated at 147 million euro (US$233). CONCLUSIONS: This study shows that the costs of screening and management of CIN represent a heavy burden to the public health system in Spain.

Epidemiology and cost of treatment of genital warts in Spain.

BACKGROUND: Genital warts (GW) are common and increasing in young people. Ninety percent of GW are due to Human Papillomavirus (HPV) types 6 and 11. The objective of this study was to assess the epidemiology and management costs associated with GW in Spain. METHODS: A 1-year (2005) retrospective observational study was performed among a sample of gynaecologists, dermatologists and urologists in six autonomous regions in Spain. Men and women with newly diagnosed, recurrent or resistant GW were included. We estimated the incidence (new and recurrent cases) and prevalence (also including resistant cases) of GW. Healthcare resource use were collected and combined with unit costs to assess the mean cost of GW management per patient. These figures were extrapolated to the 14- to 64-year-old Spanish population to estimate the total cost of GW management from the Third Party Payer (TPP) and societal perspectives. RESULTS: The overall annual incidence of GW was estimated at 160.4 cases per 100,000. Overall prevalence was calculated as 182.1 cases per 100,000, corresponding to 56 446 GW cases annually (14- to 64-year-old population). The mean management cost was 833 euros and 1056 euro per patient from the TPP and societal perspective, respectively. The overall annual cost was estimated at 47 million euros and 59.6 million euros, from the TPP and societal perspective, respectively. CONCLUSION: This study provides a first overview of the burden of GW in Spain. A quadrivalent HPV vaccine that prevents HPV 6, 11, 16, 18 related diseases will have the potential to significantly decrease the socio-economic burden associated with GW in Spain.

Vacuna contra el papilomavirus / No disponible

No disponible

Clinical role of cervical cancer vaccination: when and whom to vaccinate?

The recent development of two highly effective vaccines against persistent infection by the 2 most important types of human papillomavirus (HPV) (16 and 18) and against high grade premalignant lesions (CIN2+) has opened a new scenario for the primary prevention of cervical cancer. The optimum target population for vaccination should be individually defined taking the following into account: 1) the efficacy of the vaccine, 2) the epidemiological context and 3) the vaccination programs available in each country. To achieve the maximum preventive benefits, the vaccine should be administered before the initiation of sexual relations. So, the HPV vaccine should be integrated in the school vaccination programs of adolescents together with other vaccines. The vaccination of sexually active women may considerably increase the speed with which results in the fight against this disease will be achieved. Developed countries will probably consider the vaccination of these women, although vaccination strategies and the efforts to reach this population will be conditioned by the resources of each country and by the estimations of the cost-efficacy relationship in each situation. Women with a previous history of premalignant cervical disease or with an abnormal screening test should not be excluded from the potential benefits which the vaccine may provide. There is no contraindication for the administration of the vaccine in immunosupressed women. However, it is still unknown under what specific circumstances of immunosuppression the immunogenicity of the vaccine may be affected and there are currently ongoing studies for an answer to this question.

Current techniques in screening for cervical cancer in Spain: updated recommendations.

A population-based survey (AFRODITA Study) was conducted in Spain in order to estimate the coverage and factors associated with cervical cancer cytological screening. The results of this survey indicate that the rate of screening for cervical cancer in Spain is 75.6% in women between 18 and 65 years. This high rate of opportunistic cervical cancer screening possibly has increased in the last 5 years. However, screening participation still needs to be improved in older women, women living in rural areas, women at a low socioeconomic level, and women living in certain autonomous regions. Conversely, an overuse of cytology has been observed in Spain, as a result of opportunistic screening. A survey in 2005, carried out in 14 public and private Spanish cytological laboratories, showed that among 409,443 women, the mean rate of abnormal cytology (a diagnosis of at least atypical cells of undetermined significance on a Pap smear) was 3.5% with a range of 0.5%-7.0% in Spain. We believe that this low rate of abnormal Pap smears is the result of repeated annual opportunistic screening in a low-risk population of women. A new Spanish consensus protocol for screening for cervical carcinoma was developed in 2006 by the Spanish Society of Gynaecology and Obstetrics, the Spanish Association of Cervical Pathology and Colposcopy, the Spanish Society of Cytology, and the Spanish Society of Anatomic Pathology. In order to rationalize the use of cervical cancer screening in Spain, the recommendations of the new Spanish consensus screening protocol must be followed.

Coverage and factors associated with cervical cancer screening: results from the AFRODITA study: a population-based survey in Spain.

OBJECTIVE: To quantify the coverage and monitor the factors associated with opportunistic cervical cytological screening in Spain. MATERIALS AND METHODS: Population-based survey of selected women through the Access Panel technique representative of the general population. A total of 6,852 women (60%) replied to the questionnaire; 981 (14.3%) were excluded from the analysis because they did not meet the screening criteria. Data were adjusted for regions, age group, socioeconomic level (SEL), and municipality size. Moreover, information was collected on preventive gynecological revisions received. Categorical variables were evaluated through the chi2 test of heterogeneity or through a liner test for trend. Multivariate prevalence odds ratios were used to identify statistically significant determinants of screening using logistic regression modeling. RESULTS: The percentage of women 18 to 65 years old with a Pap smear within the last 3 years was 75.6%. Insufficient coverage was observed in women older than 55 years (66%), who live in rural areas (66%), with lower SEL (65%), and in some regions (61%-66%). The factors positively associated with screening were age 26 to 55 years, certain regions, higher SEL, larger municipality size, ever being pregnant, early age at first sexual intercourse, knowledge about cervical cancer and human papillomavirus, and, very strongly, ever use of contraceptive methods. An overuse of cytology can be assumed, as a result of opportunistic screening. CONCLUSIONS: In Spain, the coverage of cytological screening reached 75% of the population, but with inefficiencies in some aspects. To rationalize its use, the Spanish consensus screening protocol must be followed.

High-risk cervical epithelial neoplasia grade 1 treated by loop electrosurgical excision: follow-up and value of HPV testing.

OBJECTIVE: This study was undertaken to evaluate the value of high-risk human papillomavirus (HPV) testing in the follow-up of cervical intraepithelial neoplasia grade 1/low-grade squamous intraepithelial lesion treated by loop electrosurgical excision procedure because of the risk criteria established by the American Society for Colposcopy and Cervical Pathology (ie, unsatisfactory colposcopy or positive endocervical curettage, persistence of cervical intraepithelial neoplasia grade 1/low-grade squamous intraepithelial lesion, or high-risk HPV infection for longer than 2 years and older than 40 years). STUDY DESIGN: Seventy-seven women with cervical intraepithelial neoplasia grade 1/low-grade squamous intraepithelial lesion treated by loop electrosurgical excision procedure and followed-up with colposcopy, cytology, and high-risk HPV detection using Hybrid Capture II. RESULTS: More than 67% (67.6%) of women had cervical intraepithelial neoplasia grade 1 in the specimen; 22% a cervical intraepithelial neoplasia grade 2-3; and 10.4% had no lesion. Pretreatment HPV testing was positive in 100% of cervical intraepithelial neoplasia grade 2-3, in 93.5% of cervical intraepithelial neoplasia 1, and in 14.3% of cases with no lesion (P < .01). Pretreatment high-risk HPV testing was positive in all cases eventually developing residual/recurrent disease. Fifty percent of women with pretreatment viral load more than 100 relative light units had residual/recurrent disease develop. Posttreatment high-risk HPV testing during the follow-up reached a sensitivity and negative predictive value of 100% for detecting residual/recurrent disease. CONCLUSION: Patients with low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 and risk factors have a significant risk of harboring a cervical intraepithelial neoplasia grade 2-3 lesion. A conservative approach should be considered when basal high-risk HPV test is negative. High pretreatment high-risk HPV loads should be considered a risk factor for developing residual/recurrent disease. Posttreatment Hybrid Capture II has an extremely high sensitivity for detecting recurrences.

Pre- and post-conization high-risk HPV testing predicts residual/recurrent disease in patients treated for CIN 2-3.

OBJECTIVE: To evaluate whether high-risk human papillomavirus (HR-HPV) detection and viral load prior to treatment and status of cone margins can predict residual/recurrent disease as well as the ability of current diagnostic tools to identify residual/recurrent disease during follow-up of high-grade cervical intraepithelial neoplasia (CIN) treated by conization using loop electrosurgical procedure (LEEP). METHODS: Two hundred and three women (mean age 38.6 +/- 9.7; range 22-83) with CIN2-3 treated by LEEP conization and confirmed in the surgical specimen, attending follow-up visits were included. Age, HR-HPV detection and viral load determined by HybridCapture 2, and cone margins were evaluated as possible predictors of residual/recurrent disease. Value of single and repeated cytology as well as HR-HPV detection and viral load during follow-up were analyzed as screening tools of recurrence. RESULTS: Residual/recurrent disease was demonstrated by colposcopy guided biopsy in 36 patients (17.7%). High HR-HPV load (>1000 RLU) prior to LEEP and positive cone margins were significantly associated with higher risk of recurrence (31.8% vs. 9.4%, P = 0.005; and 36.4% vs. 11.9%, P < 0.001 respectively). HR-HPV detection at 6-12 m after LEEP showed higher sensitivity than a single or repeated cytology (97.2% vs. 83.3% and 94.4% respectively) although it showed less specificity (81.4% vs. 92.2% and 82.6%). The combination of HR-HPV detection and the first cytology during follow-up detected all patients with residual/recurrent disease (sensitivity 100%, negative predictive value 100%) with an acceptable specificity (76.6%). CONCLUSION: The inclusion of HR-HPV testing with cytology in follow-up of patients treated for CIN2-3 would allow for fewer post-treatment visits and avoid unnecessary cytologies. High HR-HPV load prior to LEEP or positive margins should be considered as risk factors for developing residual/recurrent disease.

Human papillomavirus load in Hybrid Capture II assay: does increasing the cutoff improve the test?

OBJECTIVE: The aim of the study was to evaluate whether the results of the Hybrid Capture II (HCII) assay for detecting high-grade squamous intraepithelial lesions (H-SIL) or cervical carcinoma can be improved by increasing the relative light units (RLU) level. STUDY DESIGN: We included 2271 women (mean age 38.7 +/- 12.3, range 15-92) referred to a colposcopic clinic due to cytology of atypical cells of unknown significance, SIL or carcinoma. All women underwent a new Pap test, HR-HPV detection using HCII and colposcopy with biopsy of suspicious areas when present. RESULTS: HR-HPV was detected in 91.7% of carcinomas, 96.6% of H-SIL, 85.1% of low-grade SIL and 21.6% of cases with no lesion. The probability of harboring an H-SIL or a carcinoma significantly increased as RLU increased (P = 0.01). The sensitivity and specificity for H-SIL or carcinoma at different cutoffs were 95.7 and 54.6 at 1 RLU, 93.9 and 59.6 at 2 RLU, 90.1 and 65.1 at 5 RLU and 85.7 and 68.7 at 10 RLU. The percentage of cases not detected with HCII increased from 2.4% for cases with <1 RLU to 9.5% for cases between 1 and 2 RLU, 14.8% between 2 and 3 RLU, 21.7% between 3 and 5 RLU and 28.4% between 5 and 10 RLU. CONCLUSION: The use of a higher cutoff (higher viral load) in the HCII should not be recommended because it significantly increases the number of cases with H-SIL or carcinoma not detected, reducing the sensitivity and negative predictive value of the test.

The use of sentinel lymph nodes in gynaecological malignancies.

PURPOSE OF REVIEW: Lymphatic mapping and sentinel node biopsy represent one of the most revolutionary advances in oncological surgery in recent years. In this review, the current state of sentinel node detection in gynaecological cancers and its use in vulvar and cervical cancer are assessed. RECENT FINDINGS: Since the recent clinical application of sentinel node biopsy for melanomas and breast cancer, there has been extensive research on the implementation of this technique to most solid neoplasias. Studies on the feasibility of sentinel node biopsy in vulvar cancer have shown that the status of the sentinel node is an accurate predictor of the status of inguinal nodes. The clinical implementation of the procedure requires validation and is under investigation. In the last two years, several pilot studies on the feasibility of lymphatic mapping/sentinel node biopsy in cervical cancer have yielded promising results. There is minimal experience of its use in endometrial cancer. Detailed pathological study of a sentinel node biopsy with ultrastaging and immunohistochemical or polymerase chain reaction analyses can identify lymph node micrometastasis that conventional methods would identify as negative for metastatic disease. The best histopathological procedure for sentinel node biopsy, the clinical significance of micrometastases, and the appropriate management of such micrometastases are currently under investigation. SUMMARY: Sentinel node biopsy is one of the main research interests in gynaecological oncological surgery. At present there are not enough data to permit modification of current treatment protocols. Large and multi-institutional trials are required in order to define the implementation of sentinel node biopsy in clinical practice with the objective of achieving safer and more conservative surgery.

Prospective evaluation of squamous cell carcinoma and carcinoembryonic antigen as prognostic factors in patients with cervical cancer.

Carcinoembryonic antigen (CEA) and squamous cell carcinoma(SCC) serum levels were prospectively determined in 159 untreated patients diagnosed with carcinoma of the uterine cervix from 1991 to 2001. The histological analysis showed epidermoid cancer in 117 patients, adenocarcinoma in 26 patients, adenosquamous carcinoma in 12 patients and other histological types in the remaining 4 patients. Tumor marker sensitivity was related to the histological type with abnormal SCC (>2 ng/ml) in 51.3% of squamous tumors in contrast to the 7.1% found in other histologies. By contrast, CEA sensitivity was not related to histology with abnormal values (>5 ng/ml) in 25% of squamous tumors, 19% of adenocarcinomas, 33% of adenosquamous carcinomas and 25% of other histologies. CEA and SCC serum levels were clearly related to tumor stage, parametrial invasion, tumor size and nodal involvement. Elevated pretreatment CEA indicates parametrial invasion with a probability of 82%. Likewise, pretreatment CEA and SCC serum levels were of prognostic value, with a shorter disease-free survival and overall survival in patients with abnormal levels. All patients with adenocarcinomas and abnormal CEA had relapse during follow-up. Multivariate analysis indicated that parametrial invasion, age, tumor size and SCC were independent prognostic factors. In conclusion, CEA and SCC are useful tumor markers in carcinomas of the uterine cervix, with a clear relationship with well-known prognostic factors (parametrial invasion, nodal involvement), and are of prognostic value.

Further data on the usefulness of sentinel lymph node identification and ultrastaging in vulvar squamous cell carcinoma.

OBJECTIVE: The aim was to determine the feasibility of surgical identification and pathological ultrastaging of sentinel nodes (SNs) in vulvar carcinoma and to evaluate whether SN negativity rules out the possibility of metastasis in other nodes and can therefore avoid conventional lymphadenectomy. MATERIAL AND METHODS: In 26 patients with vulvar squamous cell carcinoma the SNs were detected using both peritumoral injection of (99m)Tc and blue dye (isosulfan or methylene) before the surgical procedure. Dissection of the SNs was followed by standard lymphadenectomy and vulvar exeresis. For pathological ultrastaging at least eight histological sections of every node separated 400 microm were evaluated using hematoxylin & eosin and immunostaining against cytokeratin. RESULTS: We identified the SNs in 25/26 patients (96%). In 19 patients (76%) the SN was unilateral and in 6 (24%) it was bilateral. A total of 46 SNs were isolated. Metastatic carcinoma was identified in 9 SNs from 8 patients (30.8%). Thirty-eight percent (3 of 8) patients with metastatic SNs presented micrometastasis detected only in ultrastaging. Seven (3.3%) of 239 nonsentinel nodes (non-SNs) showed metastasis. No metastatic implant was detected in non-SNs when SNs were negative in patients without clinical suspicious adenopathy (100% negative predictive value). CONCLUSION: Inguinofemoral lymph nodes can be confidently avoided when sentinel node metastases are excluded by histological ultrastaging. This may reduce the surgical morbidity of conventional inguinofemoral lymphadenectomy, without worsening vulvar cancer prognosis.

Is vascular and lymphatic space invasion a main prognostic factor in uterine neoplasms with a sarcomatous component? A retrospective study of prognostic factors of 60 patients stratified by stages.

BACKGROUND: Sarcomatous neoplasms of the uterine corpus are still a challenge in terms of obtaining prognostic factors and the most optimum complementary treatment to surgery. The most important prognostic factor is stage; relapses usually appear during the first 2 years, and most patients die within the first 3 years. We have performed a multivariate study of prognostic factors, stratifying patients by stage, to determine their impact on overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival. Special emphasis has been given to vascular and lymphatic space invasion (VLSI). METHODS: Sixty patients diagnosed with uterine neoplasms with a main sarcomatous component were treated at Hospital Clínic i Universitari of Barcelona between January 1975 and June 1999. Pathologic type: 32 carcinosarcomas, 14 leiomyosarcomas, 9 adenosarcomas, and 5 endometrial stromal sarcomas. TREATMENT: 58/60 surgery, 35/60 postoperative radiotherapy, 2/60 exclusive chemotherapy, and 3/60 complementary chemotherapy. FIGO stages: 43 Stage I, 4 Stage II, 11 Stage III, and 2 Stage IV. Variables analyzed: age, stage, vascular and lymphatic space invasion, myometrial invasion, mitotic index, tumor size, unicentricity/multicentricity, necrosis, and radiotherapy. STATISTICS: the S and Cox proportional risk models. The partial effect of each risk factor was calculated by hazard ratio (HR) with a confidence interval of 95%. RESULTS: Early stages: Multivariate analysis showed that tumor size larger than 8 cm and VLSI had an impact on overall survival (HR = 4.01 and HR = 24.45, respectively). VLSI was present in 23% of the cases. Myometrial invasion greater than 50% had an impact on disease-free survival and local relapse-free survival (HR was 9.75 and 3.20, respectively). VLSI had an impact on distant metastasis-free survival (HR = 2.92). Advanced stages: VLSI was present in 89% of the cases. Only leiomyosarcoma type made the overall survival worse (HR = 10.54). CONCLUSIONS: Vascular and lymphatic space invasion was a relevant prognostic factor in our series, with an impact on overall survival and distant metastasis-free survival in early stages. In advanced stages, VLSI had no impact on survival, but was present in 89% of cases. Myometrial invasion >50% had an impact on local relapse. Advanced stages had a more aggressive behavior, and there was a higher incidence of poor prognostic factors in these stages. Nevertheless, prospective studies are still needed on prognostic factors and on the best treatment option.

Neoplasias intraepiteliales multicéntricas en tracto genital inferior : estudio retrospectivo / Multicentrical genital intraepithelial neoplasia in inferior genital tract

A mil trecientas cinco pacientes se les diagnosticó neoplasia intraepitelial del tracto genital inferior (NITGI); de las cuales, a 26 pacientes (2 por ciento ) se les diagnosticó neoplasia intraepitelial multicéntrica. El promedio de edad se situó en 42,1 años, con una mínima de 20 y un máximo de 89 años. De todas las pacientes con NITGI, 1239 (93,2 por ciento ) correspondieron a una neoplasia intraepitelial cervical (CIN), 26 (2,1 por ciento ) estuvieron asociadas con neoplasia intraepitelial vulvar (VIN), 13 (18 por ciento ) fueron asociados con neoplasia intraepitelial cervical o vaginal. Diez y ocho pacientes (1 por ciento ) presentaron neoplasia intraepitelial vaginal (VAIN), 11 (61,1 por ciento ) se asociaron con neoplasia intraepitelial cervical o vulvar. La lesiones intraepiteliales multicéntricas, se presentaron en un 65,3 por ciento de forma metacrónica, consistente a su vez con el 62,0 por ciento de lesiones severas (grado III) histológicas. La infección por HPV, so obervó en el 50 por ciento de los casos, y las pacientes con antecedente de HIV (+) se encontró en el 23 por ciento , estableciéndose diferencias significativas, en su relación con la edad de las pacientes. Nuestros resultados soportan la idea, de que una deficiente inmunidad puede asociarse con la infección por HPV, condilomas, precánceres en presentación multicéntrica, o lesiones invasivas del tracto genital inferior