RESUMO
In Costa Rica (CR), only one report on head and neck cancer (HNC) incidence trends (1985-2007) has been published and no investigations on the epidemiology of potentially human papillomavirus (HPV)-related and HPV-unrelated HNCs have been done. We examined the age-standardized incidence rates (IRs) and trends of head and neck squamous cell carcinomas (HNSCC) and compared incidence trends of potentially HPV-related and HPV-unrelated HNSCCs. We obtained all available HNC cases for the period 2006-2015 from the Costa Rican National Cancer Registry of Tumors and the population estimates from the Costa Rican National Institute of Statistics and Census. The analysis was restricted to invasive HNSCCs (n = 1577). IRs and incidence rate ratios were calculated using SEER*Stat software and were age-standardized for the 2010 Costa Rican population. Joinpoint regression analysis program was used to calculate trends and annual percent changes (APCs) in rates. For all HNSCCs, the age-standardized IR was 34.0/million person-years; 95% CI 32.4, 35.8. There was a significant decline in the incidence of nasopharyngeal cancer (APC: -5.9% per year; 95% CI -10.8, -0.7) and laryngeal cancer (APC: -5.4% per year; -9.2, 1.5). The incidence trends for hypopharyngeal, oropharyngeal and oral cavity cancers each remained stable over time. HNSCCs were categorized by their potential relatedness to HPV infection. Though the APCs were not statistically significant, IRs of potentially HPV-related HNSCCs trended upward, while HPV-unrelated HNSCCs trended downward. HNSCCs are uncommon in CR and decreased over time. We observed a divergent pattern of decreasing HPV-unrelated with increasing HPV-related HNSCCs that should be further informed by HPV genotyping tumor samples.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Nasofaríngeas , Infecções por Papillomavirus , Humanos , Adulto , Carcinoma de Células Escamosas de Cabeça e Pescoço , Incidência , Papillomavirus Humano , Costa RicaRESUMO
BACKGROUND: We investigated the impact of human papillomavirus (HPV) vaccination on the performance of cytology-based and HPV-based screening for detection of cervical precancer among women vaccinated as young adults and reaching screening age. METHODS: A total of 4632 women aged 25-36 years from the Costa Rica HPV Vaccine Trial were included (2418 HPV-vaccinated as young adults and 2214 unvaccinated). We assessed the performance of cytology- and HPV-based cervical screening modalities in vaccinated and unvaccinated women to detect high-grade cervical precancers diagnosed over 4 years and the absolute risk of cumulative cervical precancers by screening results at entry. RESULTS: We detected 95 cervical intraepithelial neoplasia grade 3 or worse (52 in unvaccinated and 43 in vaccinated women). HPV16/18/31/33/45 was predominant (69%) among unvaccinated participants, and HPV35/52/58/39/51/56/59/66/68 predominated (65%) among vaccinated participants. Sensitivity and specificity of cervical screening approaches were comparable between women vaccinated as young adults and unvaccinated women. Colposcopy referral rates were lower in the vaccinated group for HPV-based screening modalities, but the positive predictive value was comparable between the 2 groups. CONCLUSIONS: Among women approaching screening ages, vaccinated as young adults, and with a history of intensive screening, the expected reduction in the positive predictive value of HPV testing, associated with dropping prevalence of HPV-associated lesions, was not observed. This is likely due to the presence of high-grade lesions associated with nonvaccine HPV types, which may be less likely to progress to cancer.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Costa Rica/epidemiologia , Detecção Precoce de Câncer/métodos , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Adulto JovemRESUMO
BACKGROUND: Oncogenic human papillomavirus (HPV) infections cause most cases of cervical cancer. Here, we report long-term follow-up results for the Costa Rica Vaccine Trial (publicly funded and initiated before licensure of the HPV vaccines), with the aim of assessing the efficacy of the bivalent HPV vaccine for preventing HPV 16/18-associated cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: Women aged 18-25 years were enrolled in a randomised, double-blind, controlled trial in Costa Rica, between June 28, 2004, and Dec 21, 2005, designed to assess the efficacy of a bivalent vaccine for the prevention of infection with HPV 16/18 and associated precancerous lesions at the cervix. Participants were randomly assigned (1:1) to receive an HPV 16/18 AS04-adjuvanted vaccine or control hepatitis A vaccine. Vaccines were administered intramuscularly in three 0·5 mL doses at 0, 1, and 6 months and participants were followed up annually for 4 years. After the blinded phase, women in the HPV vaccine group were invited to enrol in the long-term follow-up study, which extended follow-up for 7 additional years. The control group received HPV vaccine and was replaced with a new unvaccinated control group. Women were followed up every 2 years until year 11. Investigators and patients were aware of treatment allocation for the follow-up phase. At each visit, clinicians collected cervical cells from sexually active women for cytology and HPV testing. Women with abnormal cytology were referred to colposcopy, biopsy, and treatment as needed. Women with negative results at the last screening visit (year 11) exited the long-term follow-up study. The analytical cohort for vaccine efficacy included women who were HPV 16/18 DNA-negative at vaccination. The primary outcome of this analysis was defined as histopathologically confirmed CIN2+ or cervical intraepithelial neoplasia grade 3 or worse associated with HPV 16/18 cervical infection detected at colposcopy referral. We calculated vaccine efficacy by year and cumulatively. This long-term follow-up study is registered with ClinicalTrials.gov, NCT00867464. FINDINGS: 7466 women were enrolled in the Costa Rica Vaccine Trial; 3727 received the HPV vaccine and 3739 received the control vaccine. Between March 30, 2009, and July 5, 2012, 2635 women in the HPV vaccine group and 2836 women in the new unvaccinated control group were enrolled in the long-term follow-up study. 2635 women in the HPV vaccine group and 2677 women in the control group were included in the analysis cohort for years 0-4, and 2073 women from the HPV vaccine group and 2530 women from the new unvaccinated control group were included in the analysis cohort for years 7-11. Median follow-up time for the HPV group was 11·1 years (IQR 9·1-11·7), 4·6 years (4·3-5·3) for the original control group, and 6·2 years (5·5-6·9) for the new unvaccinated control group. At year 11, vaccine efficacy against incident HPV 16/18-associated CIN2+ was 100% (95% CI 89·2-100·0); 34 (1·5%) of 2233 unvaccinated women had a CIN2+ outcome compared with none of 1913 women in the HPV group. Cumulative vaccine efficacy against HPV 16/18-associated CIN2+ over the 11-year period was 97·4% (95% CI 88·0-99·6). Similar protection was observed against HPV 16/18-associated CIN3-specifically at year 11, vaccine efficacy was 100% (95% CI 78·8-100·0) and cumulative vaccine efficacy was 94·9% (73·7-99·4). During the long-term follow-up, no serious adverse events occurred that were deemed related to the HPV vaccine. The most common grade 3 or worse serious adverse events were pregnancy, puerperium, and perinatal conditions (in 255 [10%] of 2530 women in the unvaccinated control group and 201 [10%] of 2073 women in the HPV vaccine group). Four women in the unvaccinated control group and three in the HPV vaccine group died; no deaths were deemed to be related to the HPV vaccine. INTERPRETATION: The bivalent HPV vaccine has high efficacy against HPV 16/18-associated precancer for more than a decade after initial vaccination, supporting the notion that invasive cervical cancer is preventable. FUNDING: US National Cancer Institute.
Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Vacinas Combinadas/administração & dosagem , Adolescente , Adulto , Costa Rica , Método Duplo-Cego , Feminino , Humanos , Imunização , Gradação de Tumores , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vacinas Combinadas/efeitos adversos , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
Testing negative for human papillomavirus (HPV) predicts long-term reassurance against invasive cervical cancer (ICC). To provide realistic estimates of effectiveness for new screening programs, we studied ICC risk after a 7-year repeated multimethod screening effort. In 1993-1994, 10,049 women aged 18-97 years were enrolled into a population-based cohort study of cervical HPV in Guanacaste, Costa Rica. Women were screened at different intervals according to enrollment results. Each visit (mean 3.2, 90% attendance) included split-sample conventional, automated, and liquid-based cytology, visual inspection, cervicography, and PCR-based HPV testing. Abnormal screening led to colposcopy and excisional treatment as appropriate during the study. Referral to colposcopy for HPV in the absence of other findings was introduced only at the last visit. Population-based Costa Rica Cancer Registry linkage identified cohort women diagnosed with ICC in the 18 years following cohort enrollment. The ICC cumulative risk was 0.4% (n = 38); 18 were diagnosed with ICC after study participation. Of these, 9 were missed at the screening step (negative screening or below the referral threshold, refused screening or colposcopy), 5 attended colposcopy but were not diagnosed as CIN2+, and 4 were treated for CIN2/3 but progressed to ICC nonetheless. Decreasing age-standardized ICC rates for the 1993-2011 period were observed in Guanacaste; cohort women showed additional 31% ICC incidence reduction with apparent downstaging of cancers that occurred. ICC risk following negative HPV testing in the optimal age range 30-50 years was extremely low. Real-life screening effectiveness following introduction is lower than the potential near-complete efficacy predicted by HPV natural history.
Assuntos
Citodiagnóstico , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Colposcopia , Costa Rica , DNA Viral/isolamento & purificação , Feminino , Seguimentos , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Gravidez , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Esfregaço VaginalRESUMO
The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 2010, which randomized 7466 women aged 18 to 25 to receive the bivalent HPV-16/18 vaccine or control Hepatitis-A vaccine. Participants were followed for 4 years with cross-over vaccination at the study end. In 2010 the long term follow-up (LTFU) study was initiated to evaluate the 10-year impact of HPV-16/18 vaccination, determinants of the immune response, and HPV natural history in a vaccinated population. Herein, the rationale, design and methods of the LTFU study are described, which actively follows CVT participants in the HPV-arm 6 additional years at biennial intervals (3 additional study visits for 10 years of total follow-up), or more often if clinically indicated. According to the initial commitment, women in the Hepatitis-A arm were offered HPV vaccination at cross-over; they were followed 2 additional years and exited from the study. 92% of eligible CVT women accepted participation in LTFU. To provide underlying rates of HPV acquisition and cervical disease among unvaccinated women to compare with the HPV-arm during LTFU, a new unvaccinated control group (UCG) of women who are beyond the age generally recommended for routine vaccination was enrolled, and will be followed by cervical cancer screening over 6 years. To form the UCG, 5000 women were selected from a local census, of whom 2836 women (61% of eligible women) agreed to participate. Over 90% of participants complied with an interview, blood and cervical specimen collection. Evaluation of comparability between the original (Hepatitis-A arm of CVT) and new (UCG) control groups showed that women's characteristics, as well as their predicted future risk for cervical HPV acquisition, were similar, thus validating use of the UCG. LTFU is poised to comprehensively address many important questions related to long-term effects of prophylactic HPV vaccines.
Assuntos
Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Costa Rica/epidemiologia , Estudos Cross-Over , Detecção Precoce de Câncer , Feminino , Seguimentos , Vacinas contra Hepatite A/administração & dosagem , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/imunologia , Projetos de Pesquisa , Fatores de Tempo , Doenças do Colo do Útero/epidemiologia , Doenças do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , Vacinação , Adulto Jovem , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/prevenção & controleRESUMO
BACKGROUND: Self-collected human papillomavirus (HPV) testing could reduce barriers to cervical cancer screening, with performance comparable to clinician-collected specimens. The ability of self-collected specimens to cross-sectionally and prospectively detect precursor lesions was investigated in an HPV vaccine randomized trial in Costa Rica. METHODS: In the trial, 7466 women age 18 to 25 years received an HPV16/18 or control vaccine and were followed at least annually for four years. In this secondary analysis, we included all women who provided a self-collected cervicovaginal specimen six months after enrollment (5109 women = full analytical cohort). A subset (615 women = restricted cohort) also had clinician-collected specimens at the six-month postenrollment visit. High-grade squamous intraepithelial lesion or repeat low-grade squamous intraepithelial lesion prompted colposcopic referral throughout the study. HPV testing was performed with SPF10PCR/DEIA/LiPA25. Cross-sectional and prospective sensitivity, specificity, and predictive values were estimated. RESULTS: In the full cohort, one-time HPV testing on self-collected samples detected prevalent CIN2+ with a sensitivity of 88.7% (95% confidence interval [CI] =77.0% to 95.7%) and a specificity of 68.9% (95% CI = 67.6% to 70.1%). For predicting incident CIN2+ in the subsequent four years, sensitivity was 73.9% (95% CI = 65.8% to 81.0%) and specificity 69.4% (95% CI = 68.1% to 70.7%). In the restricted cohort, for incident CIN2+, self-collected HPV was much more sensitive than cytology (80.0% vs 10.0%); relative sensitivity was 0.1 (95% CI = 0.03% to 0.5%). Furthermore, three times more women with normal baseline cytology developed incident CIN2+ than those with negative self-collected HPV. Self-collected and clinician-collected HPV testing had comparable performance. Agreement between self- and clinician-collected samples was 89.7% (kappa = 0.78, McNemar χ2 = 0.62) for carcinogenic HPV types. CONCLUSIONS: Self-collected specimens can be used for HPV-based screening, providing sensitivity and specificity comparable with clinician-collected specimens and detecting disease earlier than cytology.
Assuntos
Alphapapillomavirus/isolamento & purificação , DNA Viral/análise , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Lesões Pré-Cancerosas/virologia , Manejo de Espécimes/métodos , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto , Idoso , Alphapapillomavirus/genética , Estudos de Coortes , Colposcopia , Costa Rica , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Vacinas contra Papillomavirus/administração & dosagem , Lesões Pré-Cancerosas/prevenção & controle , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/prevenção & controleRESUMO
Carcinogenic human papillomavirus (HPV) infections are very common after sexual debut and nearly all become undetectable ("clear") within a few years. Following clearance, the long-term risks of type-specific HPV re-appearance and subsequent risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) are not well defined. In the 7-year, population-based cohort study in Guanacaste, Costa Rica, we studied how often type-specific carcinogenic HPV infections re-appeared after clearance and how often re-appearance led to CIN2+. We considered 1,740 carcinogenic HPV infections detected by MY09/11 PCR among 2,805 women (18-91 years old, median 34) who were actively followed at 6- or 12-month intervals. We identified women with one or more type-specific HPV infections that cleared and re-appeared and further defined a subgroup of "definite clearance and re-appearance" (≥2 intervening negative results over a period of ≥1 year). We determined the absolute risk of CIN2+ among the different groups. p values are two-sided. Only 7.7% (81/1,052) of HPV-infected women had intervening negative results. Very few (3.7%, 39/1,052) had "definite clearance and re-appearance", of which 5.1% (2/39) subsequently persisted to a diagnosis of CIN2. There were zero CIN3+ lesions. Extremely few women (2/2,805 of women in our cohort) had a type-specific carcinogenic HPV infection clear, re-appear and lead to CIN2+. If confirmed, this argues against vaccination to avoid re-appearance that leads to precursor lesions and against the need of frequent HPV screening after initial negative results.
Assuntos
Papillomaviridae/classificação , Infecções por Papillomavirus/virologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , DNA Viral/genética , Feminino , Seguimentos , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Gradação de Tumores , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , Adulto Jovem , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologiaRESUMO
BACKGROUND: The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease. METHODS: At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and > or =42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided. RESULTS: Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and > or =42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent infections among older women (> or =42 years) was higher than that among younger age groups or new infections at any age (P < .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse. CONCLUSIONS: The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.
Assuntos
Alphapapillomavirus/isolamento & purificação , Infecções por Papillomavirus/complicações , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Carga Viral , Adulto , Fatores Etários , Colposcopia , Costa Rica/epidemiologia , Detecção Precoce de Câncer , Feminino , Humanos , Estudos Longitudinais , Programas de Rastreamento , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Reação em Cadeia da Polimerase , Medição de Risco , Fatores de Risco , Fatores de Tempo , Neoplasias do Colo do Útero/epidemiologia , Adulto Jovem , Displasia do Colo do Útero/epidemiologiaRESUMO
OBJECTIVE: To evaluate the cumulative incidence of cervical intraepithelial neoplasia II or worse (grade II+) or cervical intraepithelial neoplasia grade III+ after short term persistence of prevalently detected carcinogenic human papillomavirus (HPV). DESIGN: Population based cohort study. SETTING: Guanacaste, Costa Rica. PARTICIPANTS: 2282 sexually active women actively followed after enrolment. MAIN OUTCOME MEASURES: Primary end points: three year and five year cumulative incidence of histologically confirmed cervical intraepithelial neoplasia grade II+ (n=70). Cervical specimens collected at each visit tested for more than 40 HPV genotypes. HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82 were considered the primary carcinogenic genotypes. RESULTS: Women who tested positive for a carcinogenic HPV at enrolment and after about one year (9-21 months) (positive/positive) had a three year cumulative incidence of cervical intraepithelial neoplasia grade II+ of 17.0% (95% confidence interval 12.1% to 22.0%). Those who tested negative/positive (3.4%, 0.1% to 6.8%), positive/negative (1.2%, -0.2% to 2.5%), and negative/negative (0.5%, 0.1% to 0.9%) were at a significantly lower risk. There was little difference in the cumulative incidence of cervical intraepithelial neoplasia grade II+ between testing positive twice for any carcinogenic HPV genotype (same genotype or different genotypes) v testing positive twice for the same carcinogenic genotype (17.0% v 21.3%, respectively). Short term persistence of HPV 16 strongly predicted cervical intraepithelial neoplasia grade II+, with a three year cumulative incidence of 40.8% (26.4% to 55.1%). Similar patterns were observed for the five year cumulative incidence of grade II+ and for three year and five year cumulative incidence of grade III+. CONCLUSIONS: Short term persistence of a prevalently detected carcinogenic HPV infection, especially HPV 16, strongly predicts a subsequent diagnosis of cervical intraepithelial neoplasia II+ over the next few years.
Assuntos
Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Costa Rica/epidemiologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Lesões Pré-Cancerosas/virologia , Fatores de Risco , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/virologiaRESUMO
A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993-1994. At the enrollment visit, we applied multiple state-of-the-art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography. Any positive screening test led to colposcopic referral and biopsy and/or excisional treatment of CIN2 or worse. We retrospectively tested stored specimens with an early HPV test (hybrid capture tube test) and for >40 HPV genotypes using a research PCR assay. We followed women typically 5-7 years and some up to 11 years. Nonetheless, 16 cases of invasive cervical cancer were diagnosed during follow-up. Six cancer cases were failures at enrollment to detect abnormalities by cytology screening; 3 of the 6 were also negative at enrollment by sensitive HPV DNA testing. Seven cancers represent failures of colposcopy to diagnose cancer or a precancerous lesion in screen-positive women. Finally, 3 cases arose despite attempted excisional treatment of precancerous lesions. Based on this evidence, we suggest that no current secondary cervical cancer prevention technologies applied once in a previously under-screened population is likely to be 100% efficacious in preventing incident diagnoses of invasive cervical cancer.