Francesca Maria Carozzi

Istituto per lo Studio e la Prevenzione Oncologica (ISPO), Florence, Tuscany, Italy

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Publications (13)27.56 Total impact

  • Article: HPV type distribution in invasive cervical cancers in Italy: pooled analysis of three large studies.
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    ABSTRACT: OBJECTIVE: The aim of this study is to describe the prevalence of HPV types in invasive cervical cancers in Italy from 1996 to 2008. METHODS: A pooled analysis of the three largest case series typed to date was performed. HPV typing was performed on paraffin-embedded slices. Molecular analyses were performed in four laboratories. Multivariate analyses were performed to test the associations between calendar time, age, and geographical area and the proportion of types 16/18. RESULTS: Out of 574 cancers, 24 (4.2%) were HPV negative. HPV 16 and 18 were responsible for 74.4% (378/508) and 80.3% (49/61) of the squamous cancers and adenocarcinomas, respectively. Other frequent types were 31 (9.5%), 45 (6.4%), and 58 (3.3%) for squamous cancers and 45 (13.3%), 31, 35, and 58 (5.0%) for adenocarcinomas. The proportion of HPV 16 and/or 18 decreased with age (p-value for trend <0.03), while it increased in cancers diagnosed in more recent years (p-value for trend < 0.005). CONCLUSIONS: The impact of HPV 16/18 vaccine on cervical cancer will be greater for early onset cancers. In vaccinated women, screening could be started at an older age without reducing protection.
    Infectious Agents and Cancer 10/2012; 7(1):26.
  • Article: [Human Papilloma Virus (HPV), cervical cancer incidence and screening uptake: differences among Northern, Central and Southern Italy].
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    ABSTRACT: this article presents a review of evidences about Human Papillomavirus (HPV) and cervical cancer in Italy, highlighting geographical differences. two systematic reviews recently published were updated, one collecting studies on the prevalence of HPV types in Italy in the general population and the other collecting prevalence of HPV types in cervical pathologic samples.The search was updated to 31.10.2010 and performed exclusively in MedLine and references in retrieved papers. the prevalence of HPV types has been related with the incidence of cervical cancer and the spread of Pap tests and screening programs. the prevalence high risk HPV types is 8%in studies with population-based random sample, with no significant difference between Centre-North and South-Islands, however, the prevalence is slightly higher in the South than the Centre-North for women up to 54 years of age, whereas in older women the ratio is reversed. HPV 16 is the most common type, while HPV 18 is less frequent, 5% and 1% respectively. The average of HPV 16 positivity is 64% and 68% in CIN2/3 and invasive cancer respectively, while the average of HPV 18 is 7% and 11% in CIN2/3 and invasive cancer respectively. There are no significant differences by geographical area.The incidence of invasive cervical cancer in Italy has been decreasing in recent years changing from 9.2 to 7.7 per 100,000 inhabitants in 10 years. The incidence is lower in South-Islands. Pap test coverage is over 80% in Centre-North and less than 60%in South-Islands. cervical cancer incidence is lower in Southern Italy, while the Pap test coverage is much higher in Centre-Northern Italy. This paradox, until now, has been interpreted as a consequence of a lower HPV prevalence in Southern than Northern regions. Recent studies on HPV prevalence do not confirm this hypothesis. Our interpretation is that in Southern Italy we are facing an epidemiologic scenario in transition where the low cancer incidence is the consequence of a low HPV prevalence in the previous decades, but new generations are experiencing a higher prevalence of HPV and will probably have higher risk of cervical cancer. The consequence may be an epidemic of cervical cancer in the next decades, if adequate screening programs are not implemented.
    Epidemiologia e prevenzione 03/2012; 36(2):108-19. · 0.65 Impact Factor
  • Article: Molecular profile in body fluids in subjects enrolled in a randomised trial for lung cancer screening: Perspectives of integrated strategies for early diagnosis
    Lung Cancer 05/2010; 68(2):216-21. · 3.43 Impact Factor
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    Article: Prevalence of HPV high and low risk types in cervical samples from the Italian general population: a population based study.
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    ABSTRACT: This multicenter study describes the type-specific prevalence of HPV infection in the general population from central and southern Italy, comparing the data with previously published Italian studies. Women aged from 25 to 65 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11. 3817 women had a valid HCII test: 350 of them (9.2%) were positive for HR probes, 160 (4.2%) for LR probes, while 57 women were positive for both. Multiple infections were detected in 97 HR HPV positive women. The most common types were HPV 16 (3%), 31 (1.2%), 51 (1%). HPV6 ranked fifth (0.6%), HPV18 ranked tenth (0.5%) and HPV11 sixteenth (0.3%).In Sardinia the prevalence of high-risk infection was 13%, significantly higher than the mean value (p < 0.00005).The distribution of the most frequent types did not significantly differ by centre (p = 0.187) and age (p = 0.085). Because cervical cancer incidence and Pap test coverage is lower in southern than in northern Italy, a lower prevalence of high-risk infections in the general population was expected in the south. However, prevalence detected in this study for the south of the country is slightly but significantly higher than the rest of Italy. The consequence may be an epidemic of cervical cancer in the next decades if adequate screening programs are not implemented there.
    BMC Infectious Diseases 01/2010; 10:214. · 3.12 Impact Factor
  • Article: Is human papillomavirus screening preferable to current policies in vaccinated and unvaccinated women? A cost-effectiveness analysis.
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    ABSTRACT: Italy was the first European nation to offer free vaccination against human papillomavirus (HPV) types 16 and 18. The vaccination is actively encouraged and is available free of charge to 11-year-old girls. The introduction of new technologies such as HPV DNA testing and HPV vaccination requires cost-effectiveness analysis of cervical cancer strategies in Italy for both vaccinated and unvaccinated women. A calibrated Markov model was developed to describe the natural history of HPV infection and cervical carcinogenesis. We performed a microsimulation generating the life histories of 10 million women. Changes in these life histories occur as consequences of prevention strategies. We estimated costs of screening activities using an activity-based costing analysis. We assessed lifetime risk due to cervical cancer, lifetime costs and quality-adjusted life-expectancy (QALE) for 18 scenarios. Strategies varied by screening interval (three and five years), primary and triage test (Pap test and HPV DNA test), and HPV 16 and 18 vaccination. The current screening policy (Pap test every three years) is more costly and less effective than HPV DNA test and Pap test triage every five years. For unvaccinated women an HPV DNA test every five years with a Pap test triage was cost-effective (ICER €5753/QALE). Vaccination followed by the same screening strategy was cost-effective (ICER €23,951/QALE) for women who are eligible to be vaccinated. Our findings strongly support changing the Pap screening policy to the use of HPV DNA as a primary test with Pap test triage for both vaccinated and unvaccinated women.
    Journal of Medical Screening 01/2010; 17(4):181-9. · 1.69 Impact Factor
  • Article: Molecular profile in body fluids in subjects enrolled in a randomised trial for lung cancer screening: Perspectives of integrated strategies for early diagnosis.
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    ABSTRACT: The aim of this study was to evaluate the diagnostic value of a grid of molecular genetic markers detectable in sputum and plasma samples of individuals enrolled in a lung cancer screening program with low-dose CT. Subjects enrolled in the baseline screening round of the ITALUNG (randomised) screening trial were invited to provide biological specimens for molecular analysis (1356 subjects out of 1406). We included 98 subjects in this analysis. There was a highly statistically significant difference between proportion of subjects with a negative baseline CT screening test who were positive to allelic imbalance, and those with a non-calcified nodule (NCN greater than or equal to 5mm), the reason of recall for all suspects at CT Scan (chi(2): 22.9; P<0.0001). Allelic imbalance showed good performance for screening of NCN > or = 5 mm. In subjects recalled for NCN > or = 5 mm, LOH, K-ras mutations and high levels of free plasma DNA (>5ng/ml plasma) might be important to support clinical decision making for further follow-up and repeated screening. This study, embedded in an early diagnosis randomised trial, suggests that a multi-screening approach integrating imaging technique and a biomolecular marker panel is worth of further investigation.
    Lung cancer (Amsterdam, Netherlands) 07/2009; 68(2):216-21. · 3.14 Impact Factor
  • Article: Design, recruitment and baseline results of the ITALUNG trial for lung cancer screening with low-dose CT.
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    ABSTRACT: Results of randomized clinical trials (RCTs) are needed to assess the efficacy of lung cancer screening with low-dose chest computed tomography (CT) in reducing lung cancer mortality. We report design and results of enrolment and baseline screening test in the ITALUNG trial, a RCT. Invitation letters were sent to subjects of 55-69 years of age clients of 269 general practitioners. Smokers or former smokers of at least 20 pack/years were eligible and after written consent were randomized in an active arm undergoing a low-dose CT annually for 4 years and in a control arm receiving no screening. Management of positive screening test was carried out using follow-up low-dose CT, fluorodeoxyglucose positron emission tomography, fine needle aspiration cytology and fiber optic bronchoscopy. A sample of 3206 eligible subjects was achieved by sending 71,232 letters (enrolment efficacy = 4.5%). Subjects in control (n = 1593) and active (n = 1613) arm were balanced for age, gender and smoking history. Two-hundred and seven (12.8%) subjects did not undergo CT after randomization. The baseline screening test was positive in 426 (30.3%) of 1406 subjects. Twenty-one lung cancers (prevalence = 1.5%) were found in 20 subjects: 18 non-small cell lung cancer (NSCLC), 2 small cell lung cancer (SCLC) and a case of typical carcinoid. Ten NSCLC (47.6%) were in Stage I. Sixteen fine needle aspirations were performed in 15 lung cancers, with a positive result in 12 (75%) cases. One biopsy only (6.3%) was performed on a benign lesion. Seventeen lung cancers (81%) were treated with surgical resection in 16 subjects. One subject underwent surgery for a benign lesion (5.5% of all surgical resections). Recruitment by mail of high risk subjects for a lung cancer screening RCT is feasible but not efficient. Results of the baseline screening test in the active arm of the ITALUNG trial are substantially in line with those of RCT and observational studies.
    Lung Cancer 09/2008; 64(1):34-40. · 3.43 Impact Factor
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    Article: Combined analysis of HPV DNA and p16INK4a expression to predict prognosis in ASCUS and LSIL pap smears.
    Francesca Maria Carozzi
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    ABSTRACT: Human papillomavirus (HPV) is known to play an important etiological role in the genesis of cervical cancer, but only a very small proportion of infected women develop invasive cervical cancer. The purpose of cervical cancer prevention is early diagnosis of its precursors. The molecular detection of HPV DNA as a diagnostic test to cervical carcinogenesis gave a low positive predictive value as compared to the use of biomarkers. p16INK4a has been proposed as putative surrogate biomarkers that would allow identification of dysplastic cervical epithelia. Serial consecutive cervical smears were test for high-risk HPV stained with immunocytochemistry for p16INK4a and followed-up for 36 months. The aim of the study was to evaluate the immunohistochemical expression of pl6INK4a as a marker of progression risk in low-grade dysplastic lesions of the cervix uteri. In the present series, significant pl6 overexpression was observed in the group that progressed from low to high-grade squamous intraepithelial lesion when compared with the group that did not progress. In conclusion, overexpression of p16INK4a acts as potential biomarkers for cervical cancer progression from premalignant lesions.
    Collegium antropologicum 05/2007; 31 Suppl 2:103-6. · 0.61 Impact Factor
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    Article: Prognostic significance of p53 and Ki-67 antigen expression in surgically treated non-small cell lung cancer: immunocytochemical detection with imprint cytology.
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    ABSTRACT: The purpose of this study was to determine the prognostic significance of the expression of p53 and Ki-67 in non-small cell lung cancer (NSCLC) using immunocytochemical detection. All consecutive NSCLC cases were selected for study, and, after surgery, a part of each tumor sample was frozen at -20 degrees C and stored for immunocytochemical studies. Overexpression of p53 was associated significantly with worse patient outcome in stage I disease, whereas no excess risk was evident in stage II and III cases. The same pattern was observed for Ki-67 expression. The excess risk in stage I cases with p53 and Ki-67 overexpression was observed only in adenocarcinoma. These findings are in agreement with other retrospective studies and support the hypothesis that p53 alteration may have different roles in adenocarcinoma and in squamous cell carcinoma, such as a carcinogenic factor for both cellular types but progression only for adenocarcinoma.
    American Journal of Clinical Pathology 04/2006; 125(3):425-31. · 2.60 Impact Factor
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    Article: Reproducibility of HPV DNA Testing by Hybrid Capture 2 in a Screening Setting.
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    ABSTRACT: Within a large Italian randomized trial on new technologies for cervical cancer screening involving 7 laboratories with different levels of experience, an intralaboratory and interlaboratory quality control program for human papillomavirus (HPV) DNA testing by Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) was implemented. To monitor the hybridization and detection steps, target samples containing purified, concentration-defined, HPV DNA were introduced in each test run. Only 3 of 1,024 showed a mistake in a positive vs negative classification with a 1 relative light unit (RLU)/positive control specimen (PC) ratio cutoff. To monitor the preanalytic steps (particularly denaturation), blinded specimens (33 collected in PreservCyt (Cytyc, Boxborough, MA) and 36 in Specimen Transport Medium (STM, Digene) were centrally prepared, divided into aliquots, and sent to each laboratory. The multiple-rater scores for negative (<1 RLU/PC), low-positive (1 to <11 RLU/PC), and high-positive (> or =11 RLU/PC) samples, respectively, were 0.91, 0.60, and 0.69 with PreservCyt and 0.93, 0.87, and 0.90 with STM. Our data showed high reliability and reproducibility with HC2, with values higher for STM than ThinPrep (Cytyc) samples.
    American Journal of Clinical Pathology 11/2005; 124(5):716-21. · 2.60 Impact Factor
  • Article: Triage with human papillomavirus testing of women with cytologic abnormalities prompting referral for colposcopy assessment.
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    ABSTRACT: The current study was conducted to evaluate the cost-effectiveness of triaging for colposcopy using human papillomavirus (HPV) testing. HPV tests were performed in a consecutive series of women who were referred for colposcopy for persistent atypical squamous cells of undetermined significance (ASCUS)-favor reactive (n = 35 women), ASCUS-favor squamous epithelial lesion (n = 164 women), atypical glandular cells of undetermined significance (n = 74 women), low-grade squamous epithelial lesion (n = 161 women), or high-grade squamous epithelial lesion (n = 78 women). The cost effectiveness of triaging women with ASCUS results using HPV testing was determined compared with the current protocol. The sensitivity of HPV testing for cervical intraepithelial neoplasia > Grade 2 was very high. Cost analysis showed a moderate increase in cost with the addition of HPV triage. Because HPV testing is highly sensitive, it may be useful as an alternative to the current policy of 6-month repeat cytology for women with ASCUS.
    Cancer 02/2005; 105(1):2-7. · 4.77 Impact Factor
  • Article: [Biological basis for HPV vaccines].
    Francesca Maria Carozzi
    Epidemiologia e prevenzione 31(2-3):92-9. · 0.65 Impact Factor
  • Article: Conventional pap smear and liquid-based cervical cytology smear: comparison from the same patient.
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    ABSTRACT: The results of blind reading of smears obtained with liquid-based cytology in patients previously screened by conventional cytology were compared. Cases selected for the study were a consecutive series of 99 subjects undergoing colposcopy within the screening program of the Florence District. The Pap test samples were processed utilizing the Thin Prep 2000 (Cytyc Corporation, Boxborough, MA). The liquid-base cytology smears were randomly admixed and read by seven expert cytologists with more than 15 years of experience in Pap smear reading. For each case, a consensus diagnosis was created and considered as the definitive diagnosis. Cytologic reports in conventional and liquid-based cytology smears were compared by the kappa statistic to evaluate diagnostic agreement. The study showed that the conventional and liquid-based cytology provide comparable cytologic reports and that the latter is not less sensitive than the former in detecting CIN2+ lesions of the cervix. Such evidence suggests the feasibility of randomized studies comparing the two methods, which are needed before adopting liquid-based cytology as the current method when screening for cervical cancer.
    Tumori 88(4):288-90. · 0.86 Impact Factor