The performance of mobile screening units in a breast cancer screening program in Brazil.

PURPOSE: In Brazil, access to breast cancer screening outside of urban centers is limited. This study aims to describe the coverage and performance of a breast cancer screening program implemented with Mobile Screening Units (MSU) in northern São Paulo state. METHODS: This is a retrospective cohort study of a population-based mammography program targeting women ages 40-69 in 108 municipalities from 12/2010 to 07/2015. Screening coverage rates were estimated using the Brazil 2010 census data. We calculated performance measures for the number of exams, recalls, and detected cases of cancer. Screen-detected cases were compared to clinically detected cases using hospital cancer registry data and a propensity-score matching method. The down-staging of screen-detected cases relative to clinically detected cases was assessed using logistic regression to calculate risk ratios (RRs) with 95% confidence intervals. RESULTS: 122,634 women were screened through the MSU program, representing a cumulative coverage rate of 54.8% in the target population. For initial and subsequent rounds, recall rates were 12.25 and 6.10% and cancer detection rates were 3.63 (95% CI 3.23-4.10) and 1.94 (95% CI 1.59-2.41), respectively. 92.51% of referrals were successful. Screen-detected cases had more favorable prognoses than clinically detected cases, including smaller tumor size and a decreased risk of late-stage detection (RR 0.14 95% CI 0.074-0.25). CONCLUSIONS: MSUs are a feasible method for the delivery of mammography services in this setting. Patients who had breast cancer detected on an MSU had favorable prognostic factors when compared with clinically detected cases arising from the same target population.

Assortative mixing as a source of bias in epidemiological studies of sexually transmitted infections: the case of smoking and human papillomavirus.

For studies examining risk factors of sexually transmitted infections (STIs), confounding can stem from characteristics of partners of study subjects, and persist after adjustment for the subjects' individual-level characteristics. Two conditions that can result in confounding by the subjects' partners are: (C1) partner choice is assortative by the risk factor examined and, (C2) sexual activity is associated with the risk factor. The objective of this paper is to illustrate the potential impact of the assortativity bias in studies examining STI risk factors, using smoking and human papillomavirus (HPV) as an example. We developed an HPV transmission-dynamic mathematical model in which we nested a cross-sectional study assessing the smoking-HPV association. In our base case, we assumed (1) no effect of smoking on HPV, and (2) conditions C1-C2 hold for smoking (based on empirical data). The assortativity bias caused an overestimation of the odds ratio (OR) in the simulated study after perfect adjustment for the subjects' individual-level characteristics (adjusted OR 1·51 instead of 1·00). The bias was amplified by a lower basic reproductive number (R 0), greater mixing assortativity and stronger association of smoking with sexual activity. Adjustment for characteristics of partners is needed to mitigate assortativity bias.

The road ahead for cervical cancer prevention and control.

Since the early 1950s, Papanicolaou ("Pap") cytology screening has dramatically reduced cervical cancer mortality in most high-income settings. Currently, human papillomavirus (hpv) vaccination has the greatest potential to reduce the global burden of cervical cancer and precancerous lesions. However, as the prevalence of precancerous lesions declines, maintaining cytology as the primary screening test in settings with established programs might become less efficient. A reduction in test performance (sensitivity, specificity, and positive predictive value) would lead to an increase in unnecessary colposcopy referrals. Fortunately, hpv dna testing has emerged as a suitable candidate to replace cytology. Compared with the Pap test, hpv testing is less specific but much more sensitive in detecting high-grade precancerous lesions, less prone to human error, and more reproducible across settings. Linkage of hpv vaccination and screening registries could serve the added role of monitoring vaccine efficacy. As a triage test, cytology is expected to perform with sufficient accuracy because most hpv-positive smears would contain relevant abnormalities. This approach and others-for example, hpv testing followed by genotyping-are being evaluated in large population studies and have already been recommended in some settings. Other specific biomarkers that might perform well for screening and triage include hpv E6/E7 messenger rna testing, methylation of host or viral genes, and p16(INK4a) staining. Considering the rapid pace of major discoveries and the anticipated arrival of a nonavalent hpv vaccine (currently in phase iii trials), the evidence base in this field has become an elusive target and will continue to be an obstacle for policymakers.

Screening histories and contact with physicians as determinants of cervical cancer risk in Montreal, Quebec.

BACKGROUND: Cervical cancer (cca) is largely a preventable disease if women receive regular screening, which allows for the detection and treatment of preinvasive lesions before they become invasive. Having been inadequately screened is a common finding among women who develop cca. Our primary objective was to determine the Pap screening histories of women diagnosed with cca in Montreal, Quebec. Secondary objectives were to determine the characteristics of women at greatest risk of cca and to characterize the level of physician contact those women had before developing cca. METHODS: The Invasive Cervical Cancer Study, a population-based case-control study, consisted of Greater Montreal residents diagnosed with histologically confirmed cca between 1998 and 2004. Respondents to the 2003 Canadian Community Health Survey and a sample of women without cca obtained from Quebec medical billing records served as controls. RESULTS: During the period of interest, 568 women were diagnosed with cca. Immigrants and women speaking neither French nor English were at greatest risk of cca. Most of the women in the case group had been screened at least once during their lifetime (84.8%-90.4%), but they were less likely to have been screened within 3 years of diagnosis. Having received care from a family physician or a medical specialist other than a gynecologist within the 5 years before diagnosis was associated with a greater risk of cca development. CONCLUSIONS: Our findings provide evidence of the need for an organized population-based screening program. They also underscore the need for provider education to prevent missed opportunities for cca screening when at-risk women seek medical attention.

Assessment of the performance of algorithms for cervical cancer screening: evidence from the Ludwig-McGill cohort study.

OBJECTIVE: There are currently multiple tests available for cervical cancer screening and the existing screening policies vary from country to country. No single approach will satisfy the specific needs and variations in risk aversion of all populations, and screening algorithms should be tailored to specific groups. We performed long term risk stratification based on screening test results and compared the accuracy of different tests and their combinations. METHODS: A longitudinal cohort study of the natural history of HPV infection and cervical neoplasia enrolled 2462 women from a low-income population in Brazil. The interviews and cervical screening with cytology and HPV DNA testing were repeated according to a pre-established protocol and the subjects were referred for colposcopy and biopsy whenever high grade lesions were suspected. We compared the specificity, sensitivity and predictive values of each screening modality. Long term risk stratification was performed through time-to-event analyses using Kaplan-Meier analysis and Cox regression. RESULTS: The best optimization of sensitivity and specificity was achieved when using dual testing with cytology and HPV DNA testing, whereby the screening test is considered positive if either component yields an abnormal result. However, when allowing 12months for the detection of lesions, cytology alone performed nearly as well. Risk stratification revealed that HPV DNA testing was not beneficial for HSIL cases, whereas it was for ASCUS and, in some combinations, for negative and LSIL cytology. CONCLUSION: Our results suggest that some high risk populations may benefit equally from cytology or HPV DNA testing, and may require shorter intervals between repeat testing.

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study.

BACKGROUND: Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented. METHODS: The three arms are: Control arm - liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years. RESULTS: A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+. CONCLUSION: After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial.

OBJECTIVES: To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. METHODS: We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed. RESULTS: Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9-13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45-0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels. CONCLUSIONS: Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women.

Who's Not Protected in the Herd? Factors Associated with Vaccine-Type HPV in Unvaccinated Women.

STUDY OBJECTIVE: Evidence suggests that vaccine-type human papillomavirus (HPV) prevalence may decrease in unvaccinated women after HPV vaccine introduction, indicating herd protection. The aim of this study was to determine factors associated with vaccine-type HPV (i.e. absence of herd protection) after vaccine introduction. DESIGN: We conducted three cross-sectional studies from 2006-2014 (n = 1180): wave 1 (2006-2007), wave 2 (2009-2010), and wave 3 (2013-2014). SETTING: Participants were recruited from a hospital-based teen health center and a community health department. PARTICIPANTS: We recruited 13-26 year-old young women; those included in this analysis had not received an HPV vaccine. INTERVENTIONS AND MAIN OUTCOME MEASURES: The outcome measure was infection with at least one vaccine-type HPV (HPV6, 11, 16, 18). RESULTS: Multivariable logistic regression demonstrated that in wave 1 (before vaccine introduction), history of anal intercourse (OR = 1.8, 95% CI = 1.1-3.0), age 18-21 vs 13-17 years (OR = 2.1, CI = 1.2-3.6), and Black/multiracial vs White race (OR = 1.8, CI = 1.1-3.0) were associated with vaccine-type HPV in unvaccinated women. In wave 2, no variables were associated with HPV. In wave 3, sexually transmitted infection history (OR = 3.6, CI = 1.3-9.7) was associated with HPV. CONCLUSION: We did not identify a consistent set of modifiable risk factors associated with vaccine-type HPV after vaccine introduction across the three study waves, underscoring the urgency of vaccination for primary HPV prevention and the limitations of relying on herd protection.

Epidemiologic correlates of cervical neoplasia and risk of human papillomavirus infection in asymptomatic women in Brazil.

To investigate whether the epidemiologic correlates of cervical cancer are predictors of infection with genital human papillomavirus (HPV), we performed a prevalence survey in two metropolitan areas of Brazil, Recife and São Paulo. The data records of four randomly selected HPV-negative women were matched on the basis of age, clinic, and admission period with those of each of 136 patients with positive HPV DNA hybridizations. Anal intercourse [prevalence rate ratio (PRR) = 1.7] and current pregnancy (PRR = 2.3) were the only variables associated with HPV 6/11 infection (P less than .10). Only the frequency of gynecologic consultations was associated (negatively) with risk of HPV 16/18 infection (P = .0175). Our data failed to provide evidence for the existence of shared risk factors for genital HPV infection and cervical cancer. The frequency of mixed HPV infections was 13 times higher than expected, a finding suggestive of the existence of additional determinants of HPV infection not akin to the general behavioral characteristics of women that are probed in the study.

Independent prognostic value of laminin receptor expression in breast cancer survival.

We studied the possible prognostic role of laminin, estrogen (ER), and progesterone (PR) receptors and other pathological factors in relation to the disease-free interval and overall survival of female breast carcinoma patients. Multivariate analyses of clinical and pathological data with respect to the above survival time variables were performed by Cox regression. The statistical dependence of prognosis on ER, PR, and tumor size was based on the discriminant cutoff value that could best distinguish between survival curves. Axillary nodal status was the most significant independent factor in the prediction of both disease-free interval and overall survival of these patients. Use of the information on laminin receptor expression, PR concentration, tumor size, lymphocytic infiltrate, and tumor necrosis improved significantly the prediction of the risk of recurrence. Patients with tumors expressing laminin receptors had 40% less risk of recurrence (P = 0.0209) than those with no expression. On the other hand, four covariates were independently predictive of the risk of death: axillary nodal status, lymphocytic infiltrate, PR and ER concentration. There was a marginally significant (10% level) interaction between tumor size and lymphocytic infiltrate with respect to the prediction of the risk of recurrence. The above sets of variables were used to classify patients into risk groups for the prediction of recurrence and death.

Risk behaviour change and HIV infection among injection drug users in Montreal.

OBJECTIVE: To investigate the independent association between changes in risk behaviour and HIV seroconversion risk among Montreal injection drug users (IDU). DESIGN: A longitudinal study of risk behaviour change and the maintenance of low-risk practices. At baseline and semi-annually, subjects were tested for HIV, and questionnaires on risk behaviour were completed. RESULTS: A total of 833 IDU were recruited from January 1992 to June 1998, and completed a minimum of three visits. Large fluctuations in risk behaviour were observed, and the risk of HIV infection appeared to be dependent upon the consistency of risk behaviour practised. IDU who consistently engaged in risky behaviour were at high risk of HIV infection. IDU who attempted to practise low-risk behaviour but experienced relapses to risky behaviour were also at considerable risk of infection. IDU who managed to maintain low-risk practices were at minimal risk. Using Cox regression analysis, the hazard ratio (HR) of HIV seroconversion among IDU who consistently and inconsistently shared needles with an HIV-positive partner was 8.17 (95% CI 3.59-18.59) and 2.63 (95% CI 1.33-5.17), respectively, relative to non-needle sharers. Corresponding HIV incidence rates were 30.42 per 100 person-years (py) among consistent sharers, 13.78 per 100 py among inconsistent sharers and 2.51 per 100 py among non-sharers. CONCLUSION: Although some HIV risk reduction was evident, behaviour change seems to be effective only in IDU who adopt and maintain low-risk practices. Additional strategies may be needed to assist IDU in the maintenance of low-risk practices.

Prognostic value of human papillomavirus in the survival of cervical cancer patients: an overview of the evidence.

Some studies have suggested that the presence in tumors of nucleic acids from human papillomavirus (HPV) constitutes a prognostic marker of disease severity in cervical cancer. There are two conflicting lines of evidence in this regard. First, the presence of HPV 18 is equated to rapid progression through early disease stages, possibly resulting in a more aggressive clinical course. Although fragmentary, in terms of the clinical and epidemiological basis, this line of evidence has some experimental support. Second, the absence of HPV from the tumor would confer a worse prognosis than if any viral types were present. Unlike the former, the latter line of evidence is not bolstered by experimental data but emerged from persuasive clinical studies, which had adequate sample sizes, used survival end points, and controlled for confounders. The absence of HPV in some tumors could indicate that they originated through different oncogenic mechanisms, perhaps resulting in different cell proliferation rates and, consequently, distinct clinical behavior. On the other hand, HPV detectability could simply be a correlate of other genuine prognostic characteristics, which would explain its association with survival. Both the nature and the mechanism of the prognostic role for HPV in cervical cancer remain to be elucidated. The paucity of studies can be attributed to the labor-intensive nature of assays for HPV. It is hoped that the advent of the polymerase chain reaction method will facilitate the conduct of retrospective studies of archival histopathology specimens and survival information.(ABSTRACT TRUNCATED AT 250 WORDS)

Human papillomavirus testing for primary screening of cervical cancer precursors.

Our objective was to determine whether the addition of human papillomavirus (HPV) testing to screening cytology improves the detection of cervical cancer precursors. Women of ages 18-69 years underwent conventional Pap cytology and HPV DNA testing in a multicenter study in Newfoundland, Canada. Those with positive cytology and/or HPV and a random sample of those with dual negative results were referred for colposcopy. The study enrolled 2098 women. The relative sensitivity of HPV testing was significantly higher than cytology for all-grade squamous intraepithelial lesions [SILs; 73%; 95% confidence interval (CI), 62-82] and high grade SILs (HSILs; 90%; 95% CI, 74-97) but had lower relative specificity (62% for all-grade SILs and 51% for HSILs) than most cytological cutpoints. The rate of combined correct results for all-grade lesions was higher for HPV testing (68.8%) than for any cytological cutpoint (equivocal, 52.3%; LSILs, 51.6%; HSILs, 44.5%). The combination of HPV and an LSIL cutpoint had a negative predictive value of 68% (95% CI, 52-80) for all SILs and 100% (95% CI, 91-100) for HSILs, while referring for colposcopy only 12% of the women. We concluded that HPV testing in conjunction with cytology improved the screening efficacy of cytology alone and may allow for a more effective and safe primary screening program with increased screening intervals.

Major histocompatibility complex class II polymorphisms and risk of cervical cancer and human papillomavirus infection in Brazilian women.

Infection with high-risk human papillomavirus (HPV) is the major risk factor for the development of malignant lesions in the uterine cervix. Environmental, behavioral, and ill-defined genetic factors also have been implicated in the pathogenesis of this disease. Associations between human leukocyte antigens (HLAs) and cervical cancer, precursor lesions, and HPV infections have been reported in several populations. To verify whether HLA-DRB1, -DQA1, and -DQB1 diversity is related to cervical cancer in the Brazilian population, 161 cases and 257 controls were HLA typed. Variants of DQA1 and DQB1 promoter regions were also typed in 92 cases and 228 controls. Polymorphism in HLA genes and promoters was distinguished by PCR-based methods, and the magnitude of associations was determined by logistic regression analysis. DRB1*15 [confounder-adjusted odds ratio (OR), 2.24; 95% confidence interval (CI), 1.29-3.90], DRB1*1503 (OR, 2.52; 95% CI, 1.16-5.48), and haplotype DRB1*15-DQB1*0602 (OR, 2.04; 95% CI, 1.15-3.61) were positively associated with cervical cancer. When we considered only DR15 haplotypes that did not carry the DQB1*0602 allele, the risk attributed to DRB1*15 more than doubled. A negative association was found between DQB1*05 and cervical cancer (OR, 0.57; 95% CI, 0.35-0.92), and similar trends were observed for DQA1*0101/04, DRB1*0101, and DRB1*1302. HPV positivity among controls was associated with DRB1*1503 (OR, 4.60; 95% CI, 1.33-15.9), DRB1*0405 (OR, 6.21; 95% CI, 1.66-23.2), and DQB1*0602 (OR, 2.48; 95% CI, 1.06-5.80). We suggest that HLA class II polymorphisms are involved in genetic susceptibility to cervical cancer and HPV infection in a Brazilian population from an area with a high incidence of this neoplasia.

A cumulative case-control study of risk factor profiles for oncogenic and nononcogenic cervical human papillomavirus infections.

Human papillomaviruses (HPVs) play an essential role in the etiology of cervical cancer, but besides an established role for sexual transmission, little is known about other risk factors for HPV infection. Risk factors for nononcogenic, oncogenic, and HPV 16 cervical infections were investigated using a cumulative case-control approach nested in an ongoing cohort study of low income women from São Paulo, Brazil. HPV DNA was detected and typed by the MY09/11 PCR protocol. Risk factor information was obtained via interviews. In a case-control analysis, we compared women who harbored infections with exclusively nononcogenic types (n = 123), exclusively oncogenic types (n = 94), and any HPV 16 (n = 60) to women remaining HPV-negative (n = 512) throughout 1 year of follow-up. A strong negative association was found between age and oncogenic infections, but not with nononcogenic infections. Oral contraceptive use was strongly and exclusively associated with oncogenic and HPV 16 infections. Markers of sexual activity were associated with all types of infections, although with varying strengths. Our results suggest some important differences in the epidemiological correlates of HPV infection according to oncogenicity that may have implications for the-planning of specific preventive strategies aiming at reduction of cervical cancer risk.

Computer-assisted multiple categorization of absorbance values in ELISA through pictorial emulation of 96-well plates.

A simple algorithm is proposed by which multiple categorization of absorbance values from ELISA plates is performed under a microcomputer control. The printed output is a pictorial emulation of a 96-well plate with the color intensities represented for each reaction. Although the method is presented as a colorimeter computer interfaced system, a provision for manual entry of absorbance values via keyboard is also included. Simulation is based solely on the magnitude of absorbance values. Therefore, it is possible to utilize any enzyme/substrate combination within the range of filters of the colorimeter. We have tested the present system for titration of anti-malarial antibodies in human serum and for the screening of mouse hybridoma culture supernatants.

Multiple cancers of the upper aero-digestive tract: the challenge of risk factor identification.

Carcinomas of the upper aero-digestive tract (UADT) are among the most common neoplasms, particularly in developing countries. The generally poor prognosis for UADT cancer patients is further complicated by the occurrence during follow-up of additional cancers of the same or related sites. Proper quantification of the incidence of these second cancers and characterization of their risk factors have been plagued with methodological difficulties. The effects of tobacco and alcohol consumption vary with anatomic site, which requires that matching or adjustment by site be performed in any comparisons between single primary and multiple primary patients. Clinical variables, such as disease extension, treatment and survival, also influence risk of second malignancies. However, these parameters are also strongly interrelated, which makes it difficult to characterize their individual associations with risk or to control for their confounding effects when examining other variables. These shortcomings should be taken into consideration in the design of studies searching for genetic and other inter-individual variations in susceptibility to multiple UADT malignancies.

Risk factors for second cancers of the upper respiratory and digestive systems: a case-control study.

A case-control study of determinants of multiple cancers of the upper respiratory and digestive system (URDS) was conducted using a patient cohort-nested design. We analyzed demographic and risk factor information and clinical variables related to the index cancer for 85 cases of multiple cancers and 170 controls matched on sub-site of the index cancer of the case and date of hospital admission. Follow-up information for the control group was used to infer the person-years-at-risk for the cohort of 1977 patients. URDS cancer patients experienced a 10.7 times (95% confidence interval: 8.5-13.2) higher risk of additional related cancers than the general population. Although controls had cancers of the same sites as those of cases and thus, strongly tobacco and alcohol-related, there were marked residual effects for these two risks factors. In addition, characteristics related to the extension and clinical course of the index cancer were strongly associated with the patient's risk of developing additional cancers.

Race and gender influences on the survival of patients with mouth cancer.

Previous studies have shown that race and gender are important correlates of survival among patients with cancer of certain sites. Since race and gender influence the stage of disease at diagnosis and the choice of therapy it has been argued that survival differentials may not be real but instead, they represent secondary associations with clinical variables. Therefore, verification of the true prognostic effects of race and gender requires proper controlling for potential confounders, such as stage and treatment. We have studied the 15-year survival experience of a hospital-based cohort of 4527 patients diagnosed with cancer of the mouth over a 28-year period in Brazil. Race and gender were strong predictors of stage and treatment. The odds ratios for no treatment were 1.35 (95% confidence limits [CL]: 1.09, 1.66) for females and 1.63 (CL: 1.29, 2.06) for non-white patients even after adjustment by stage, presumably a key criterion to define treatment. Survival differentials were found for lip cancer, with respect to race, and for cancers of the gum, floor of mouth, and other oral subsites, with respect to gender. Non-whites experienced 2.1 times the risk of lip cancer recurrence (CL: 1.20, 3.61) and 2.3 times the risk of dying from it (CL: 1.29, 4.09) as compared to whites. However, controlling for stage and treatment modality variables by proportional hazards regression reduced the same risk ratios to 1.01 (CL: 0.57, 1.78) and 1.17 (CL: 0.65, 2.13), respectively. The survival advantage experienced by females (17% lower risk of recurrences and 29% lower risk of cancer deaths) regarding other oral sites was independent from the effect of clinical factors.