Social determinants influencing cervical cancer diagnosis: an ecological study.

BACKGROUND: Barriers to accessing health care result in advanced cervical cancer. In Sao Paulo, Brazil, the Index of Social Responsibility (ISR) synthesizes the situation of each town concerning wealth, education, and longevity. This study aimed to evaluate in 645 municipalities the relation of the ISR with stage, age, and morphology in cervical cancer diagnosis. METHODS: An ecological study that used data from Sao Paulo, Brazil, from 2010 to 2017. The ISR was identified through government platforms and data on cancer through the Hospital Cancer Registry. The subjects were the 9,095 women aged 30 years or older. The ISR summarizes municipalities into five levels: dynamic (ISR5), unequal (ISR4), equitable (ISR3), in transition (ISR2), and vulnerable (ISR1). It was used the chi2 tests and logistic regression. RESULTS: The proportion of stage 1 increased significantly with ISR level, ranging from 24.9% in ISR1 to 30.0% in ISR5 (p = 0.040). To every increase in ISR level, the chance of a woman being diagnosed in stage I was at least 30% higher. Woman living where ISR2 had a 1.4 times higher chance of being diagnosed in stage 1 than those living in ISR1 (OR 1.40, 95% CI 1.07-1.84). Squamous tumors frequency decreased when ISR level increased (p = 0.117). A higher proportion of women under 50 years were observed when they lived in wealthier cities (ISR4 and ISR5) (42.2% vs. 44.6%, p = 0.016). CONCLUSION: The ISR was a good health indicator for understanding and predicting the social determinants in cervical cancer diagnosis. The proportion of stage I increased significantly in more favorable social conditions.

Breast Cancer Treatment Delay in SafetyNet Health Systems, Houston Versus Southeast Brazil.

BACKGROUND: Breast cancer outcomes among patients who use safety-net hospitals in the highly populated Harris County, Texas and Southeast Brazil are poor. It is unknown whether treatment delay contributes to these outcomes. METHODS: We conducted a retrospective cohort analysis of patients with non-metastatic breast cancer diagnosed between January 1, 2009 and December 31, 2011 at Harris Health Texas and Unicamp's Women's Hospital, Barretos Hospital, and Brazilian National Institute of Cancer, Brazil. We used Cox proportional hazards regression to evaluate association of time to treatment and risk of recurrence (ROR) or death. RESULTS: One thousand one hundred ninety-one patients were included. Women in Brazil were more frequently diagnosed with stage III disease (32.3% vs. 21.1% Texas; P = .002). Majority of patients in both populations had symptom-detected disease (63% in Brazil vs. 59% in Texas). Recurrence within 5 years from diagnosis was similar 21% versus 23%. Median time from diagnosis to first treatment defined as either systemic therapy (chemotherapy or endocrine therapy) or surgery, were comparable, 9.9 weeks versus 9.4 weeks. Treatment delay was not associated with increased ROR or death. Higher stage at diagnosis was associated with both increased ROR and death. CONCLUSION: Time from symptoms to treatment was considerably long in both populations. Treatment delay did not affect outcomes. IMPACT: Access to timely screening and diagnosis of breast cancer are priorities in these populations.

Real-world data on neoadjuvant endocrine therapy in ER-positive/HER2-negative breast cancer.

PURPOSE: Neoadjuvant endocrine therapy (NET) has been shown to be effective in ER-positive/HER2-negative breast cancer in clinical trials. However, adoption in clinical practice is still limited. Real-world data may provide useful insights into effectiveness, toxicities and quality of care, potentially rendering clinical trial results to the real-world setting. Our purpose was to report real-world data of a cohort of postmenopausal patients submitted to NET. METHODS: This prospective cohort study evaluated 146 postmenopausal female patients with ER-positive/HER2-negative breast cancer treated with NET at three tertiary hospitals between 2016 and 2018. Clinicopathological information were collected prospectively. Preoperative Endocrine Prognostic Index (PEPI) score was calculated for tumors submitted to at least 16 weeks of NET. RESULTS: Median age was 67 years old, and 87.8% had stage I-II disease. Most tumors had histological grade II (76.1%). Median pretreatment Ki67 expression was 10%. Aromatase inhibitor was used in 99.5% of patients, and median treatment duration was 21.0 weeks. No tumor progressed during NET. Breast-conserving surgery was performed in the majority of patients (63.0%), as well as sentinel lymph-node biopsy (76.7%). Pathological complete response rate was 1.0%. 43 patients (29.5%) had PEPI score 0, and 26% had PEPI scores 4-5. Posttreatment Ki67 median expression was 3.0%, and only five tumors (3.4%) showed marked increase in Ki67 expression during treatment. Seven patients (4.8%) had HER2-positive residual disease, and were treated with adjuvant chemotherapy plus trastuzumab. CONCLUSIONS: Our real-world data shows that NET is effective and safe in postmenopausal patients with ER-positive/HER2-negative breast cancer. Postmenopausal status and low-risk luminal tumor features (luminal A-like) should be used as selection criteria to ensure the best results with NET.

Race disparities in mortality by breast cancer from 2000 to 2017 in São Paulo, Brazil: a population-based retrospective study.

BACKGROUND: In Brazil, inequalities in access may interfere with cancer care. This study aimed to evaluate the influence of race on breast cancer mortality in the state of São Paulo, from 2000 to 2017, contextualizing with other causes of death. METHODS: A population-based retrospective study using mortality rates, age and race as variables. Information on deaths was collected from the Ministry of Health Information System. Only white and black categories were used. Mortality rates were age-adjusted by the standard method. For statistical analysis, linear regression was carried out. RESULTS: There were 60,940 deaths registered as breast cancer deaths, 46,365 in white and 10,588 in black women. The mortality rates for 100,000 women in 2017 were 16.46 in white and 9.57 in black women, a trend to reduction in white (p = 0.002), and to increase in black women (p = 0.010). This effect was more significant for white women (p < 0.001). The trend to reduction was consistent in all age groups in white women, and the trend to increase was observed only in the 40-49 years group in black women. For 'all-cancer causes', the trend was to a reduction in white (p = 0.031) and to increase in black women (p < 0.001). For 'ill-defined causes' and 'external causes', the trend was to reduce both races (p < 0.001). CONCLUSION: The declared race influenced mortality rates due to breast cancer in São Paulo. The divergences observed between white and black women also were evident in all cancer causes of death, which may indicate inequities in access to highly complex health care in our setting.

Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial.

OBJECTIVE: The present analysis determined the disease free survival (DFS) and overall survival (OS) at up to 14 years of follow-up in women who participated in our previous phase 3 randomized controlled clinical trial, in which women with stage IIIB squamous cervical cancer received either cisplatin plus RT or RT alone for treatment. The first study showed that the addition of cisplatin to RT offered a significant benefit in DFS, but not in OS. METHODS: The present analysis examined DFS and OS in 146 women from the original cohort (72 patients in the CRT arm and 74 patients in the RT-only arm) with follow-up of up to 14 years. RESULTS: Longer term follow-up showed that treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only. Patients who received RT alone had significantly worse OS (HR, 1.88; 95% CI, 1.09-3.24) and DFS (HR, 1.82; 95% CI, 1.07-3.08) compared with patients who received CRT. The multivariate analyses also showed that the patients with baseline Karnofsky performance status (KPS) <90% showed significantly worse OS (HR, 3.11; 95% CI, 1.78-5.43), as did those with hemoglobin <10 mg/dL (HR, 4.32; 95% CI, 2.23-8.36). Patients with baseline KPS < 90% showed significantly worse DFS (HR, 2.83; 95% CI, 1.60-5.01), as did those with hemoglobin <10 mg/dL (HR, 4.16; 95% CI, 2.17-7.95). CONCLUSIONS: For stage IIIB cervical cancer, treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only.

Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A in cervical cancer patient survival: a competing risk analysis.

BACKGROUND: Expression of matrix metalloproteases 2, 9 and 14 (MMP-2, MMP-9, MMP-14), tissue inhibitors of metalloprotease 1 and 2 (TIMP-1, TIMP-2) and vascular endothelial growth factor A (VEGF-A) is involved in tumor invasion and metastasis via extracellular matrix degradation and angiogenesis. This study aimed to assess whether the expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 in tumors and in the adjacent stroma is associated with cervical cancer prognosis. METHODS: This study analyzed a retrospective cohort of 64 patients. Protein expression was previously obtained by immunohistochemistry from biopsies containing both tumor and stroma. The expression and percentage of stained cells were categorized as high or low according to the cutoff points by using ROC curves. The follow-up data was collected from diagnosis to the last clinical visit. Clinical status categorized as alive without disease, alive with disease, death due to other causes, and death from the disease. The relative risk of death from the disease was evaluated according to the proteins expression using a cause-specific Cox regression model with a 95% confidence interval (95%CI). For the significant associations (p < 0.05), survival curves of patients with low and high expression were plotted for the competing risk survival curve analyses. RESULTS: High expression levels of stromal MMP-2 (RR; 95%CI: 3.91; 1.17-13.02) and stromal TIMP-2 (RR, 95%CI: 8.67; 1.15-65.27) were associated with a greater relative risk of death from the disease and with lower survival (p = 0.03; p = 0.04) than lower expression levels. Low expression levels of stromal MMP-9 (RR, 95%CI: 0.19; 0.05-0.65) and tumoral MMP-9 (HR, 95%CI: 0.19; 0.04-0.90) were protective factors against death from the disease and were associated with poorer survival. CONCLUSIONS: High expression levels of MMP-2 and TIMP-2 in the stroma were significantly associated with poor survival in cervical cancer patients. High expression of MMP-9 was associated with a favorable cervical cancer prognosis.

Cervical cancer screening program based on primary DNA-HPV testing in a Brazilian city: a cost-effectiveness study protocol.

BACKGROUND: The causal relationship between high-risk (hr) HPV infection and precancerous lesions or cervical cancer has led to the development of strategies to increase screening performance and prevent this cancer. The increased sensitivity of DNA-HPV testing compared to cervical cytology favors DNA-HPV testing as a primary screening test. Cervical cancer screening in Brazil is opportunistic, and this cancer remains a considerable health problem with a high proportion of diagnoses in advanced stages. This paper aims to describe the design and implementation of the Cervical Cancer Screening Program with primary DNA-HPV testing (CCSP-HPV) planned for Indaiatuba City (SP), Brazil; the strategies to achieve higher population coverage; and a study protocol for cost-effectiveness analyses. METHODS: The CCSP-HPV was designed based on successful guidelines that replaced cervical cytology-based screening by the DNA-HPV test performed at 5-year intervals. The screening will be performed for the female population aged 25-64 years cared for by the public health system and aim to reach 80% coverage after completing the first round. The chosen DNA-HPV test detects 14 hr-HPV types and genotypes HPV-16 and 18. All women with a negative test will be reassessed after five years. Women showing a positive test for HPV-16 and/or 18 will be referred for colposcopy. Those showing the other 12 hr-HPV types will be tested by cytology, and if any abnormality is detected, they will also be referred for colposcopy. The histopathologic evaluation will be reviewed by a pathologist panel and aided by p16 immunohistochemistry. A cost-effectiveness analysis will be performed by a Markov model comparing the cost of the new program and the screening performed by conventional cytology five years prior (2011-2016). DISCUSSION: The new screening program is considered a breakthrough for public health regarding cervical cancer, which is the third leading cause of cancer death among Brazilian women. Achieving at least 80% coverage will have the possibility to change this scenario. The proposed program will provide a modern cervical cancer screening method for women, and information about cost-effectiveness will help other similar places support the decision of implementing cervical cancer screening using the DNA-HPV test.

Prognostic assessment of breast carcinoma submitted to neoadjuvant chemotherapy with pathological non-complete response.

BACKGROUND: Breast cancer with pathological non-complete response (non-pCR) after neoadjuvant chemotherapy (NAC) has a worse prognosis. Despite Neo-Bioscore has been validated as an independent prognostic model for breast cancer submitted to NAC, non-pCR carcinoma was not assessed in this setting. METHODS: This is a retrospective trial that included women with localized breast cancer who underwent NAC and had non-pCR carcinoma in surgical specimen between 01/01/2013 to 12/31/2015 with a three-year follow-up. Survival analysis was performed by Kaplan-Meier estimator and hazard ratio (HR) set by log-rank test for the primary and secondary endpoints, respectively Disease-Free Survival (DFS) and Overall Survival (OS). According to Neo-Bioscore, the proposed prognostic model named Clustered Neo-Bioscore was classified into low (0-3), low-intermediate (4-5), high-intermediate (6) and high (7) risk. The prognostic accuracy for recurrence risk was assessed by time-dependent receiver operating characteristic (time-ROC) methodology. Multivariate Cox regression assessed the menopausal status, histological grade, Ki-67, estrogen receptor, HER2, tumor subtype, pathological and clinical stages. Confidence interval at 95% (CI95%) and statistical significance at set 2-sided p-value less than 0.05 were adopted. RESULTS: Among the 310 women enrolled, 267 patients (86.2%) had non-pCR carcinoma presenting size T3/T4 (63.3%), node-positive axilla (74.9%), stage III (62.9%), Ki-67 ≥ 20% (71.9%) and non-luminal A (78.3%). Non-pCR carcinoma presented worse DFS-3y (HR = 3.88, CI95% = 1.18-11.95) but not OS-3y (HR = 2.73, CI95% = 0.66-11.40). Clustered Neo-Bioscore discerned the recurrence risk for non-pCR carcinoma: low (DFS-3y = 0.86; baseline), low-intermediate (DFS-3y = 0.70; HR = 2.61), high-intermediate (DFS-3y = 0.13, HR = 14.05), and high (DFS-3y = not achieved; HR = 22.19). The prognostic accuracy was similar between Clustered Neo-Bioscore and Neo-Bioscore (0.76 vs 0.78, p > 0.05). Triple-negative subtype (HR = 3.6, CI95% = 1.19-10.92) and pathological stages II (HR = 5.35, CI95% = 1.19-24.01) and III (HR = 6.56, CI95% = 1.29-33.32) were prognoses for low-intermediate risk, whereas pathological stage III (HR = 13.0, CI95% = 1.60-106.10) was prognosis for low risk. CONCLUSIONS: Clustered Neo-Bioscore represents a novel prognostic model of non-pCR carcinoma undergoing NAC with a more simplified and appropriate score pattern in the assessment of prognostic factors.

Downstaging in opportunistic breast cancer screening in Brazil: a temporal trend analysis.

BACKGROUND: Breast cancer is the most common female cancer in Brazil with an estimated 60 thousand new cases per year. Widespread use of mammography opportunistic screening has been observed in the last 20 years, including women under 50 years old. The present study aimed to analyse the trends in breast cancer stage distribution at diagnosis as a function of age in the study period. METHODS: This paper examined temporal trends of stage distribution in women with breast cancer diagnosed between 2000 and 2015 in São Paulo state, Brazil. Data from the Hospital Cancer Registry of the region were utilized. Completeness was high. The sample was described according to age, stage and date of diagnosis using absolute frequency and proportions (%). For trends, the Cochran-Armitage test was used with a 5% level of significance (P-value< 0.05). RESULTS: A total of 93,674 women were included in the analysis with a median age of 56 years old. One-third (34.4%) of the women were younger than 50 years old, and stage II was the most frequent stage (36.4%), even when analysed by age groups. Stage 0 corresponded to 7.7% (7247 women) of cases. In the study period, there was a significant trend towards an increase in Stages 0, I and IV (P < 0.01) and a trend towards a decrease in Stages IIA, IIB and IIIB (P < 0.001). Stage IIA was more prevalent until 2009, and stage I was more prevalent thereafter. The trends to increase the proportion of Stages 0 and I and to decrease the proportion of stages IIA, IIB and IIIB were significant in all age groups. CONCLUSIONS: Breast cancer cases are diagnosed mainly at early stages, and approximately one-third of cases are younger than 50 years old. Downstaging has been shown. Opportunistic screening may have supported these results. Further studies are needed to show whether these results will impact the prognosis.

Estimating the public health impact of a national guideline on cervical cancer screening: an audit study of a program in Campinas, Brazil.

BACKGROUND: A Brazilian guideline on cervical cancer screening was released in 2011. The objective was to verify changes in screening indicators around this period. METHODS: An audit study which sample was all screening tests performed by the public health system of Campinas city from 2010 to 2016. Variables were absolute tests numbers, excess tests, intervals and results, by age. For trend analysis was used Cochran-Armitage × 2 and linear regression. RESULTS: Were carried out 62,925 tests in 2010 and 43,523 tests in 2016, a tendency at a reduction (P = 0.001). Excess tests were higher than 50% over the years, with a tendency at a reduction (P < 0.001). Tests performed on women under 25 ranged from 20.2 to 15.4% in the period (P < 0.001), while in the 25-64 years age-group, it ranged from 75.1 to 80.2% (P < 0.001). In 2010 the most frequent interval was annual (47.5%) and in 2016 biennial (34.7%). There was a tendency at a reduction in the proportion of tests performed at the first time and those with an annual interval (P < 0.001), and also a tendency at an increase in tests with intervals equal to or greater than biannual (P < 0.001). We observed a tendency at a reduction in LSIL and HSIL-CIN2 results (P = 0.04 and P = 0.001, respectively), and a tendency at an increase in HSIL-CIN3 result (P = 0.02). CONCLUSION: The proportion of cervical cancer screening tests performed out of the recommendation showed a significant reduction in the period. This indicates a tendency to align cervical cancer screening in Campinas with the standards recommended.

Level of human development is associated with cervical cancer stage at diagnosis.

The objective was to describe the cervical cancer cases in Brazil by the age-group and stage at diagnosis, and to associate them with the human development index (HDI), where the women live. This was a retrospective study that used data from the Brazilian hospital-based cancer registry from 2005 to 2014. The data were accessed by 5-year age/groups and the federal units. The association between the proportion of cases at Stage I and HDI was estimated in an adjusted linear regression analysis. Among the staged cases, the proportions of cases diagnosed at FIGO Stage I, II, III and IV were 21.2%, 30.7%, 39.9% and 8.2%, respectively. The cases were diagnosed mostly in women aged 45-49 years. There was a significant increase in the proportion of Stage I cases with an increasing HDI (coefficient, 0.46; 95% confidence interval, 0.17-0.76). In conclusion, most of the cases were diagnosed at late stages. The stage at the diagnosis was associated with the human development level. Impact Statement What is already known on this subject? The stage at diagnosis varies according to the level of organisation of the cancer control programme. It is expected that in well-developed programmes there will be a shift to an early stage diagnosis. What the results of this study add? The stage at a diagnosis was associated with the human development level where the women live in Brazil, where most cases were diagnosed at the late stages. What the implications are of these findings for clinical practice and/or further research? This analysis can help with better planning strategies for cancer control. Regional strategies would improve the efficiency of cancer care interventions in countries with large socioeconomic disparities.

Predictors of Pathological Complete Response in Women with Clinical Complete Response to Neoadjuvant Chemotherapy in Breast Carcinoma.

OBJECTIVE: There is insufficient information on predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast carcinoma that also presented clinical complete response (cCR) evaluated in breast, axilla and breast and axilla. METHODS: This retrospective study included 310 women with breast carcinoma who received NAC from 1/1/13 to 12/31/15 with follow-up until 8/31/16. The factors analyzed to predict pCR and cCR were menopausal status, Ki67, estrogen receptor, histologic grade, molecular subtype, tumor size, axilla status, and stage. RESULTS: The cCR/pCR rates were 53.2/16.5% (breast), 76.3/36.8% (axilla) and 50.6/13.9% (breast and axilla). Molecular subtype and HER2-positive were independent predictors to confirm pCR in women with cCR, mainly triple negative (TN) in breast (OR 22.81, 95% CI 7.13-72.96) and breast and axilla (OR 36.06, 95% CI 8.77-148.26), but not in axilla. Ki67 ≥50% expression was predictor of cCR in breast (OR 2.00, 95% CI 1.31-3.06) and breast and axilla (OR 1.67, 95% CI 1.10-1.45). CONCLUSION: TN subtype and HER2-positive were the main independent predictors of pCR in women who also had cCR to NAC in breast and breast and axilla, but none was predictor in axilla. The Ki67 ≥50% was the independent predictor of cCR in breast and breast and axilla.

Trend analysis of the quality indicators for the Brazilian cervical cancer screening programme by region and state from 2006 to 2013.

BACKGROUND: Quality indicators for the Brazilian cervical cancer screening programme can provide a perspective on its effectiveness in Brazilian macro-regions and states. The aim of this study was to perform a trend analysis of the cervical cancer screening program's quality indicators, according to Brazilian regions and states, from 2006 to 2013. METHODS: Using information from approximately 62,000,000 exams obtained from the Information System of Cervical Cancer Screening (SISCOLO), joinpoint analysis was used to calculate the Annual Percentage Change (APC). RESULTS: The estimated number of women in the target age group (25-64 years) who underwent Pap testing over a three-year interval was lower than that recommended by international guidelines in the North, Northeast and Midwest regions, and the trends for this indicator remained stationary over the years in all regions of Brazil. Overall, the index of positivity in Brazilian regions and states is below that preconized by the Brazilian National Cancer Institute (INCA). Additionally, the frequencies of unsatisfactory cases are in line with international guidelines but above those preconized by INCA guidelines. All positive cytological diagnoses were lower than those preconized by INCA. CONCLUSIONS: The results show that the cervical cancer screening programme is still far from efficient because most of the quality indicators in Brazilian regions and states are outside of the parameters preconized by national and international organizations.

Disparities in time trends of cervical cancer mortality rates in Brazil.

PURPOSE: This study aimed to correct and describe cervical cancer mortality rates and trends by regions and age-groups in Brazil. It may help planning and implementing policies for cervical cancer control. METHODS: Data from 2003 to 2012 were accessed through the centralized national mortality database. Correction of the age-specific mortality rates was done by proportional redistribution of ill-defined causes of death and deaths coded as 'uterine, part unspecified'. Annual percentage change (APC) was obtained by trend analysis (Joinpoint regression). RESULTS: In the 10-year period, cancer and ill-defined causes corresponded, respectively, to 18.9 and 10.8 % of all deaths (except injuries). The proportion of ill-defined causes was reduced by more than a half in the period. The age-standardized cervical cancer mortality rate was 7.2 per 100,000 women-years after correction. The total increase in rates after corrections was 50.5 %. A significant decreasing trend in rates was observed at the national level (APC = -0.17, p < 0.001). North was the only region that did not show a decreasing significant trend (APC + 0.07, p = 0.28). Decreasing trends were restricted to age-groups over 40 years. CONCLUSIONS: A consistent decreasing trend of cervical cancer mortality rates in Brazil from 2003 to 2012 was observed, although this was not consistent in all regions and restricted to older age-groups. Quality of data needs to be improved. Cancer control policies may consider the differences in access to care and the characteristics of regions to improve their efficiency.

Usefulness of vaginal cytology tests in women with previous hysterectomy for benign diseases: assessment of 53,891 tests.

OBJECTIVE: To assess the value of vaginal screening cytology after hysterectomy for benign disease. METHODS: This cross-sectional study used cytology audit data from 2,512,039 screening tests in the metropolitan region of Campinas from 2000 to 2012; the object was to compare the prevalence of abnormal tests in women who had undergone a hysterectomy for benign diseases (n=53,891) to that of women who had had no hysterectomy. Prevalence ratios (95% confidence intervals, 95% CI) were determined, and chi-square analysis, modified by the Cochrane-Armitage test for trend, was used to investigate the effects of age. RESULTS: The prevalence of atypical squamous cells (ASC), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion or squamous-cell carcinoma (HSIL/SCC) was 0.13%, 0.04% and 0.03%, respectively, in women who had undergone hysterectomy, and 0.93%, 0.51% and 0.26% in women who had not undergone hysterectomy. The prevalence ratios for ASC, LSIL and HSIL/SCC were 0.14 (0.11-0.17), 0.08 (0.06-0.13) and 0.13 (0.08-0.20), respectively, in women with a hysterectomy versus those without. For HSIL/SCC, the prevalence ratios were 0.09 and 0.29, respectively, for women <50 or ≥50 years. The prevalence rates in women with a previous hysterectomy showed no significant variation with age. CONCLUSION: The prevalence rates of ASC, LSIL and HSIL/SCC were significantly lower in women with a previous hysterectomy for benign disease compared with those observed in women with an intact uterine cervix. This study reinforces the view that there is no evidence that cytological screening is beneficial for women who have had a hysterectomy for benign disease.

Surgical treatment of microinvasive cervical cancer: analysis of pathologic features with implications on radicality.

OBJECTIVES: To evaluate pathologic features with implications on surgical radicality in women treated with radical hysterectomy and pelvic lymphadenectomy for cervical cancer stage IA1 with lymph vascular space invasion (LVSI) and stage IA2 by correlating findings in conization and hysterectomy specimens. METHODS: Women with cervical cancer stage IA1 with LVSI and stage IA2 diagnosed by loop electrosurgical excisional procedure or cold knife conization were treated with radical hysterectomy and pelvic lymphadenectomy from January 1999 to December 2011 in 2 institutions. RESULTS: Fifty patients were enrolled: 40 with stage IA2 and 10 with stage IA1 with LVSI. Median age was 43 (30-67) years. All patients underwent cervical conization for diagnosis (45 loop electrosurgical excisional procedure, 5 cold knife). Lymph vascular space invasion was detected in 15 patients (30%). Two patients had positive pelvic nodes. No parametrial involvement was detected in the entire cohort. Positive margins were present in 35 patients, and residual disease was detected in 22 patients (44%). Positive margins predicted residual disease at radical hysterectomy (P = 0.02). Medium follow-up time was 51 months. One patient developed a pelvic recurrence, and there were no disease-related deaths. CONCLUSIONS: Patients with positive margins in cone biopsy specimens have an increased risk of residual disease at radical hysterectomy and require careful evaluation before conservative surgery. Pelvic lymph node evaluation is essential because lymph node metastasis may occur even in early stages. The lack of parametrial invasion in this study reinforces the knowledge that the select group of patients with microinvasive cervical carcinoma stages IA1 LVSI and stage IA2 have a very low risk of parametrial infiltration. Less radical surgery can be carefully considered for these patients.

A portrait of single and multiple HPV type infections in Brazilian women of different age strata with squamous or glandular cervical lesions.

BACKGROUND: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Our objective was to assess the relationships between single- (ST) and multiple-type (MT) HPV infections with patients' age and lesion pathological status. METHODS: 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across histological types and age strata. RESULTS: 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by HPV58, 52, 31, 35 and 33. HPV18, in single or multiple infections, occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P = 0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. CONCLUSIONS: Our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18.

Protection against squamous cell carcinoma and cervical adenocarcinoma afforded by cervical cytology screening: a cross-sectional study.

OBJECTIVE: The objective of this study was to evaluate the impact of cervical cytology screening on the prevalence of cervical cytological results in women, as a function of age and test interval. METHODS: This is a cross-sectional study of cytology screening data of 2,002,472 tests obtained from previously screened women and 217,826 tests from unscreened women. The central cytopathology laboratory database was analyzed. The tests were collected for screening purposes from Campinas metropolitan region, Brazil. A prevalence ratio (PR) with a 95% confidence interval was calculated for the screened women, in relation to the unscreened women, and for different tests intervals. Protection afforded by screening (1-PR) was calculated. RESULTS: For high-grade squamous intraepithelial lesion, the PR was 0.97 (0.83-1.13) for women aged 20 years or younger and 0.99 (0.86-1.14) for women aged 20 to 24 years, decreasing significantly in women aged 25 to 29 years (PR, 0.63 [0.52-0.76]). The PR for squamous cell carcinoma, adenocarcinoma in situ (AIS), and invasive adenocarcinoma showed a significant reduction in all age groups older than 30 years. For the age group ranging from 30 to 59 years, protection for squamous cell carcinoma, AIS, and invasive adenocarcinoma was 83% or higher for screening intervals from 1 to 5 years. Protective effect was not demonstrated for screening intervals longer than 5 years for AIS and invasive adenocarcinoma. CONCLUSIONS: Cytology screening is effective at preventing cytological high-grade squamous intraepithelial lesion, squamous cell carcinoma, AIS, and invasive adenocarcinoma. On the basis of cytological results, protection against AIS and invasive adenocarcinoma was observed with screening intervals shorter than 5 years. Cytological screening in women 25 years or younger should be critically evaluated.

Microinvasive adenocarcinoma of the cervix in a young woman vaccinated against human papillomavirus: the screening must be continued.

OBJECTIVE: This report describes a case that illustrates the limitations of the vaccination screening process for human papillomavirus (HPV) infection. CASE: We report an unexpected microinvasive adenocarcinoma of the cervix arising in a young woman vaccinated against HPV as part of a clinical trial 6 years previously and followed up annually by cytology. In January 2012, at age 23 years, the patient received a cytological result of atypical squamous cells, cannot exclude high-grade cervical squamous intraepithelial lesion, and colposcopy showed slight abnormalities. Biopsy revealed an adenocarcinoma in situ. Conization of the cervix was performed, and the diagnosis was microinvasive adenocarcinoma. Polymerase chain reaction and immunohistochemical study of conization material showed positivity for HPV-18 L1, p16, and Ki-67. Retrospective analysis of the clinical trial information revealed that 7 HPV tests had been performed, and all were positive for HPV-18, including the sample collected before the first vaccination. CONCLUSIONS: HPV-18 was present in the cervix before vaccination. Persistent detection of HPV-18 should be considered an important factor in treatment planning. This case demonstrates the need to vaccinate women before their first sexual contact and highlights the need for keeping adequate screening even in vaccinated individuals.

The impact of the COVID-19 pandemic on breast cancer screening and diagnosis in a Brazilian metropolitan area.

OBJECTIVES: To evaluate the performance of breast cancer screening and early diagnosis during the pandemic, compared to the pre-pandemic period.Setting: The public referral centre for screening in Campinas, São Paulo State, Brazil. METHODS: This is an audit study of performance screening and diagnostic indicators. Two periods were analysed: 2019, the pre-COVID period, and 2020, the COVID period. All women who underwent mammography in these periods were included. Indicators were compared between periods, and the US Breast Cancer Surveillance Consortium benchmarks were used as a reference. RESULTS: A comparison between the periods shows a reduction of 57.4% in screening and 4.4% in diagnosis using mammography. Cancer detection rate per 1000 screening mammograms dropped from 4.62 to 2.83 (p = 0.031), while it increased from 84.43 to 89.36 in diagnosis mammograms (p = 0.701), higher than the reference (34.4, p < 0.001). With regard to diagnosis, the proportion of minimal cancers was reduced (p = 0.005) and was lower than the reference (40.0%, p < 0.001), along with the proportion of node-negative invasive cancers (p < 0.001). The mean size of invasive tumours was similar in the two periods (32.50 mm and 33.40 mm, p = 0.808) but larger than the reference value (16.50 mm, p < 0.001). Recall rate was lower in the COVID period (22.55% vs. 27.37%, p = 0.015). CONCLUSION: The COVID pandemic caused an overall decrease in breast screening and detection of breast cancer cases, although the reduction in number of diagnosis mammograms performed was minimal. Tumour mean size was large in both periods, the pandemic highlighting a previous profile of detection at an advanced stage.