Impact of replacing cytology with human papillomavirus testing for cervical cancer screening on the prevalence of Trichomonas vaginalis: a modelling study.

OBJECTIVES: Trichomonas vaginalis (TV) is the most common curable STI worldwide and is associated with increased risk of HIV acquisition and serious reproductive morbidities. The prevalence of TV infection is very low in Australian cities, and this is thought to be at least partly due to incidental detection and treatment of TV in women participating in the cervical cytology screening programme. In 2017, the national cervical screening programme will transition to a new model based on testing for high-risk (HR) human papillomavirus (HPV), with a reduced frequency and commencement at an older age. We model the potential impact of this transition on TV prevalence in Australia. METHODS: A mathematical model was developed to describe the transmission of TV in the general population and used to evaluate scenarios that capture the switch from cytology-based screening to HR HPV testing. Under these scenarios, individuals with asymptomatic TV who test negative for HR HPV will remain undiagnosed and untreated. We estimate the change in TV prevalence expected to occur due to the switch from cytology to HR HPV testing and changes to the frequency and age at commencement of screening. RESULTS: Our results suggest that with the transition to HR HPV testing, TV prevalence may increase from the current ~0.4% to 2.8% within 20 years if TV testing coverage is not increased and HR HPV prevalence does not decline further. If HR HPV prevalence continues to decline at its current rate with ongoing vaccination, TV prevalence is predicted to increase to 3.0% within this time frame. CONCLUSIONS: Our modelling suggests that in a setting like Australia, where TV can be detected incidentally through cytology-based cervical screening, a transition to HPV testing is likely to result in increasing TV prevalence over time unless additional measures are implemented to increase TV testing and treatment.

[New strategies for the prevention and control of cervical cancer in Chile.] / Nuevas estrategias de prevención y control de cáncer de cuello uterino en Chile.

OBJECTIVE: To discuss cervical cancer (CC), Human PapillomaVirus (HPV),CC control program and propose alternatives for Chile. MATERIALS AND METHODS: We analyzed the national program of CC 1966-2015 and the clinical CC guideline 2015-2020;HPV prevalence in women and in cases of CC; HPV infection and serology; the self-vaginal sample; the accuracy and cost-effectiveness of screening with HPV versus Papanicolaou,and triage options among HPV-AR positives. RESULTS: 600 women die of CC each year in Chile, mainly from low resources. Papanicolaou coverage is <70%; Papanicolaou sensitivity is much lowerthan HPV test.Change from Papanicolaou to HPV test is cost-effective. Since 2015, girls under 13 have been vaccinated against HPV. CONCLUSIONS: .There are the technical and economic conditions for a substantial improvement of CC in Chile: replacement of the Papanicolaou by HPV; screening every five years, with the option of self-sampling, and triage based on HPV 16/18 or Papanicolaou typing.

OBJETIVO: Discutir el cáncer cervicouterino (CC), el virus del papiloma humano (VPH),el programa de control del CC y proponer alternativas para Chile. MATERIAL Y MÉTODOS: Se analiza el programa nacional del CC 1966-2015 y la guía clínica 2015-2020, la prevalencia deVPH en mujeres y en casos de CC; la infección y serología deVPH; la autotoma; la precisión y rentabilidad del tamizaje con VPH contra el Papanicolaou y las opciones de triaje enVPH AR positivas. RESULTADOS: En Chile mueren 600 mujeres (principalmente de bajos recursos) al año por CC. La cobertura del Papanicolaou es <70%, sensibilidad muy inferior al test de VPH, por lo que el cambio esrentable.Desde 2015 se vacuna contraVPH a niñas menores de 13 años. CONCLUSIONES: Las condiciones técnicas y económicas existen en Chile para lograr una mejoría sustancial del CC:se sugiere el reemplazo del Papanicolaou por el examen deVPH;tamizaje cada cinco años con opción de autotoma; triaje con base en la tipificación deVPH 16/18 o Papanicolaou.

Use of HPV testing in cervical cancer screening services in Mexico, 2008-2018: a nationwide database study.

OBJECTIVE: To describe the methods of a study aimed at evaluating high risk-HPV (hrHPV)-based screening and cervical cytology as triage compared to conventional cervical cytology as primary screening in the detection of grade 2+ cervical intraepithelial neoplasia in the National Cancer Screening Program (NCSP) of Mexico. MATERIALS AND METHODS: We will use information originated from the Womens Cancer Information System of Mexico regarding cervical cancer from 2008 to 2018. The database includes cytology results, diagnostic confirmation by histopathology and/or treatment colposcopy. We will then carry out statistical analyses on approximately 15 million hrHPV. RESULTS: We will evaluate the overall performance of hrHPV-based screening as part of the NCSP and compare hrHPV-based to cytology-based screening under real-life conditions. To guarantee an unbiased comparison between hrHPV with cytology triage and conventional cytology we will use propensity score matching. CONCLUSIONS: ytology we will use propensity score matching. Conclusion. Decision makers may use our results to identify areas of opportunity for improvement in NCSP processe.

OBJETIVO: Describir los métodos de un estudio que busca comparar el beneficio de la introducción de la prueba de VPH de alto riesgo como prueba primaria frente a la citología convencional para la detección de la neoplasia intraepitelial cervical grado 2 o mayor, dentro del Programa de Prevención y Control del Cáncer de la Mujer, para el periodo de 2008 a 2018. MATERIAL Y MÉTODOS: Se utilizarán los registros del Sistema de Información de Cáncer de la Mujer, se realizarán los análisis estadísticos con aproximadamente 15 millones de resultados de VPH-alto riesgo, además se utilizarán los resultados de citología, colposcopia, histología y los casos referenciados al centro oncológico para tratamiento. Para comparar ambos grupos usaremos "propensity score matching". RESULTADOS: Se evaluará el desempeño general de la prueba de VPH-alto riesgo, en condiciones reales dentro del Programa Nacional de Prevención y Control de la Mujer y su tendencia en el tiempo. CONCLUSIONES: Los resultados de estudio ayudarán a los tomadores de decisiones a identificar áreas de oportunidad para mejorar el programa en México.

[Analysis of the first test of ASC-US smears by general practitioners of the Maine-et-Loire in 2014.] / Analyse du premier contrôle des frottis ASC-US par les médecins généralistes en Maine-et-Loire en 2014.

INTRODUCTION: During the study, the HAS (French Board of Health) recommended 3 options for the first test (C1) in case of presence of ASC-US: a smear to be carried out after 6 months, an HPV test or a colposcopy.Our main objective was to find out which C1 option was chosen. The secondary objectives were to evaluate the number of C1's carried out by general practitioners, the follow-up rate and that of adapted C1 smear reports. METHOD: Retrospective descriptive study based on the data obtained from CAP Santé 49 (departmental organization of cancer screening), concerning women between the ages of 25 and 65 years old having had a smear test with a positive ASC-US result carried out by a general practitioner. RESULTS: Based on 397 female patients, 373 with a 94% follow-up of which 367 C1's and 6 treatments. Among the C1's: 212 smears (57.76%), 89 tests HPV (24.25%), 40 colposcopies (10.9%), 26 double techniques (7.08%). 235 representing 64.03% were carried out by general practitioners, 130 representing 35.42% by gynecologists and 2 representing 0,54% by midwives. Of the 126 normal smear reports received by general practitioners, 70.63% gave information about an ASC-US antecedent. Among them 14 representing 15.7% complied with the recommended specified time intervals. CONCLUSION: This study which was carried out in 2014 demonstrates that HPV tests have doubled compared to a similar study carried out in 2011. In December 2016, the INCa (French National Cancer Institute) qualified this test as being the reference test for ASC-US checks. In January 2018, general cervical cancer screening involving general practitioners will be carried out. This study will serve as a basis on which to evaluate their practices.

National assessment of HPV and Pap tests: Changes in cervical cancer screening, National Health Interview Survey.

BACKGROUND: Major organizations recommend cytology screening (Pap test) every 3years for women aged 21-65; women aged 30 to 65 have the option of adding the HPV test (co-test) every 5years. We examined national percentages of cervical cancer screening, and we examined use of co-testing as an option for screening. METHODS: We used 2015 U.S. National Health Interview Survey (NHIS) data to examine recent cervical cancer screening (Pap test within 3years among women aged 21-65 without a hysterectomy; N=10,596) and co-testing (N=9,125). We also conducted a multivariable analysis to determine odds of having had a Pap test or co-test by demographic variables. To evaluate changes in screening over time, we examined Pap testing during the years 2000, 2005, 2008, 2010, 2013 and 2015. Analysis completed in Atlanta, GA during 2016. RESULTS: Overall, 81.1% of eligible women reported having a Pap test within 3years; percentages declined over time among all age groups. An estimated 14 million women aged 21-65 had not been screened within the past 3years. Recent immigrants to the United States, women without insurance, and women without a usual source of healthcare had lower odds of being up to date with screening. About 1/3 of women up to date on Pap testing reported having a co-test with their most recent Pap test. CONCLUSIONS: Declines in screening among women aged 21-65 are cause for concern. More research is needed on co-testing practices. Provider and patient education efforts may be needed to clarify recommended use of HPV tests.

[Implementation of DNA-HPV primary screening in Italian cervical cancer screening programmes. Results of the MIDDIR Project]. / L'implementazione del DNA-HPV come test primario nei programmi italiani di screening del cervicocarcinoma. Risultati del Progetto MIDDIR.

OBJECTIVES: to obtain data on conversion paths to HPV testing as part of screening programmes and to harmonize the introduction of HPV testing in primary cervical cancer screening protocols of Italian programmes. DESIGN: survey by questionnaire on strategies adopted by screening programmes for transition to primary HPV testing; systematic review of the literature; discussion among experts. SETTING AND PARTICIPANT S: managers of Italian Regions' cervical cancer screening programmes. MAIN OUTCOME MEASURES: transition planning; activity volumes; modalities of centralization; criteria for dismissal; staff training; communication initiatives. RESULTS: nine cervical screening programmes responded to the survey. Most of them chose to schedule a transition of a few years to allow for adjustment of the volume of activity in the passage from the three-year screening interval to the five-year one. To select women to be given precedence, 7 programmes use the age, starting from the oldest. The liquid base is the choice by far preferred both for HPV test and for Pap test. The reading of HPV test "born" already centralized, but a centralization process is in place also for cytology. CONCLUSIONS: the survey on conversion strategies to primary HPV testing showed the opportunity to schedule a transition phase. For HPV test, cost, organization, and quality benefits of centralization are clear, thus the central organization should be preferred and managed immediately. Moreover, the need for a centralization of cytology is evident. The tariff scheme should be based on the whole process rather than on single performances. Dismissal strategies have to be tailored on peculiarities of single services, but some typologies can be outlined.

Cervical Cancer Screening in Average-Risk Women: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians.

DESCRIPTION: The purpose of this best practice advice article is to describe the indications for screening for cervical cancer in asymptomatic, average-risk women aged 21 years or older. METHODS: The evidence reviewed in this work is a distillation of relevant publications (including systematic reviews) used to support current guidelines. BEST PRACTICE ADVICE 1: Clinicians should not screen average-risk women younger than 21 years for cervical cancer. BEST PRACTICE ADVICE 2: Clinicians should start screening average-risk women for cervical cancer at age 21 years once every 3 years with cytology (cytologic tests without human papillomavirus [HPV] tests). BEST PRACTICE ADVICE 3: Clinicians should not screen average-risk women for cervical cancer with cytology more often than once every 3 years. BEST PRACTICE ADVICE 4: Clinicians may use a combination of cytology and HPV testing once every 5 years in average-risk women aged 30 years or older who prefer screening less often than every 3 years. BEST PRACTICE ADVICE 5: Clinicians should not perform HPV testing in average-risk women younger than 30 years. BEST PRACTICE ADVICE 6: Clinicians should stop screening average-risk women older than 65 years for cervical cancer if they have had 3 consecutive negative cytology results or 2 consecutive negative cytology plus HPV test results within 10 years, with the most recent test performed within 5 years. BEST PRACTICE ADVICE 7: Clinicians should not screen average-risk women of any age for cervical cancer if they have had a hysterectomy with removal of the cervix.

Introducing a High-Risk HPV DNA Test Into a Public Sector Screening Program in El Salvador.

OBJECTIVE: In a primary human papillomavirus (HPV) screening program, we compared the 6-month follow-up among colposcopy and noncolposcopy-based management strategies for screen-positive women. MATERIALS AND METHODS: Women aged 30 to 49 years were screened with HPV DNA tests using both self-collection and provider collection of samples. Women testing positive received either (1) colposcopy management (CM) consisting of colposcopy and management per local guidelines or (2) screen-and-treat (ST) management using visual inspection with acetic acid to determine cryotherapy eligibility, with eligible women undergoing immediate cryotherapy. One thousand women were recruited in each cohort. Of these, 368 (18.4%) of 2000 women were recruited using a more intensive outreach strategy. Demographics, HPV positivity, and treatment compliance were compared across recruitment and management strategies. RESULTS: More women in the ST cohort received treatment within 6 months compared with those in the CM cohort (117/119 [98.3%] vs 64/93 [68.8%]; p < .001). Women recruited through more intensive outreach were more likely to be HPV positive, lived in urban areas, were more educated, and had higher numbers of lifetime sexual partners and fewer children. CONCLUSIONS: Women in the CM arm were less likely to complete care than women in the ST arm. Targeted outreach to underscreened women successfully identified women with higher prevalence of HPV and possibly higher disease burden.

[Cervical cancer screening with primary HPV-DNA test in the Local Health Authority 2 of Savona (Liguria Region, Northern Italy): a population-based study]. / Screening cervicovaginale con test HPV-DNA primario nella ASL 2 savonese: uno studio di popolazione.

OBJECTIVES: to describe the performance and the impact on the population coverage of a population-based organised screening programme with primary HPV-DNA test. DESIGN: population-based cohort study. SETTING AND PARTICIPANTS: organised screening programme for women aged 30-64 years. MAIN OUTCOME MEASURES: coverage of the target population with Pap test and HPV-DNA test, compliance to invitation, positivity at HPV-DNA testing, proportion of positive Pap test (squamous cells of undetermined significance or more severe, ASC-US+), referral for colposcopy, positive predictive value (PPV) of the cytology triage for grade-2 or more severe intraepithelial neoplasia (CIN2+), detection rate of CIN2+. Regarding coverage, seasonally adjusted trends of the PASSI surveillance from 2008 to 2014 were analysed. To evaluate performance, data of the information screening system were used. RESULTS: from December 2011 to December 2014, 48,852 women were invited for screening and 22,991 participated (48.4%); in addition, 968 women spontaneously participated in the programme, achieving a total of 23,959 screened women. The HPV test resulted positive for 2,000 women (8.4%). After triage 1,049 women were referred for colposcopy because of ASC-US+ (No. 968) or inadequate result (No. 81). The compliance at 12 months retesting among women with positive HPV test and negative triage was 79.3%, and the HPV positive rate was 60.4%. In the whole, 1,322 women were referred for colposcopy (5.5%) and 1,221 were actually tested. The overall detection rate for CIN2+ was 6.2/1,000. From 2011 to 2014, spontaneous Pap tests passed from 7,461/year to 2,491/year; the test coverage achieved a positive trend and it settles in recent years to 83%, including 43% of HPV-DNA. CONCLUSIONS: compliance to screening of invited women was satisfactory compared to previous experiences in Liguria Region (Northern Italy). Performance indicators confirm what was observed in other Italian experiences.

Perceived effectiveness of HPV test as a primary screening modality among US providers.

BACKGROUND: The human papillomavirus (HPV) test, administered alone without the Papanicolaou (Pap) test, was recently recognized as a cervical cancer screening option in the United States by the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology, and the Food and Drug Administration has approved an HPV test for primary screening. METHODS: Surveys of US internists, family practitioners, nurse practitioners, and obstetrician-gynecologists were conducted in 2009 and 2012 to investigate providers' perceptions of the effectiveness of the HPV test administered alone as a population-based screening modality (2009: N=1040, 141-494 per provider group; 2012: N=1039, 155-435 per provider group). RESULTS: The majority in each provider group agreed that the HPV test administered alone is an effective screening modality in 2009 (75.3%-86.1%) and 2012 (79.5%-91.8%), and agreement rose significantly during this time period among family practitioners (χ(2)=15.26, df=1, p<0.001) and nurse practitioners (χ(2)=4.53, df=1, p=0.033). CONCLUSIONS: Agreement that the HPV test administered alone is an effective cervical cancer screening modality was widespread among providers in both 2009 and 2012, however implementation of guidelines for screening with the HPV test may be influenced by many other factors including reimbursement and patient preferences.

Utilisation of co-testing (human papillomavirus DNA testing and cervical cytology) after treatment of CIN: - a survey of GPs' awareness and knowledge.

BACKGROUND: Patients have an increased risk of persistent/recurrent cervical disease if they received treatment for a high-grade squamous intraepithelial lesion (HSIL). Consequently, understanding whether co-testing (human papillomavirus [HPV] DNA testing and cervical cytology) is fully utilised by general practitioners (GPs) is paramount. METHODS: After consultation with key stakeholders, an anonymous, self-completion questionnaire was developed and disseminated to GPs who had provided cervical cytology. RESULTS: Responses were received from 745 GPs (30.9% response rate). A significant number (34.3%) of GPs were unaware of the use of co-testing (HPV DNA testing and cervical cytology) for the management of patients after HSIL treatment. Additionally, the majority of GPs reported they did not 'always' receive a clear follow-up plan for patients after treatment of an HSIL. DISCUSSION: GPs require further support and education to ensure successful adoption of co-testing (HPV DNA testing and cervical cytology), specifically, for patients treated for an HSIL.

2013 statement on human papillomavirus [corrected] test utilization.

This statement from the Cytopathology Education and Technology Consortium summarizes appropriate and inappropriate uses of human papillomavirus testing in cervical cancer screening based on guidelines from the American Society for Colposcopy and Cervical Pathology and the American Cancer Society. © 2014 S. Karger AG, Basel.

Cost analysis of different cervical cancer screening strategies in Mexico.

OBJECTIVE: To compare the costs and number of undetected cases of four cervical cancer screening strategies (CCSS) in Mexico. MATERIALS AND METHODS: We estimated the costs and outcomes of the following CCSS: a) conventional Papanicolaou smear (Pap) alone; b) high-risk human papilloma virus testing (HR-HPV) as primary screening with Pap as reflex triage; c) HR-HPV as primary screening with HPV-16/18 typing, liquid-based cytology (LBC) and immunostaining for p16/Ki67 testing as reflex triage, and d) co-testing with HR-HPV and LBC with HPV-16/18 typing and immunostaining for p16/Ki67 as reflex triage. The outcome of interest was high-grade cervical lesions or cervical cancer. RESULTS: HR-HPV testing, HPV typing, LBC testing and immunostaining is the best alternative because it is the least expensive option with an acceptable number of missed cases. CONCLUSIONS: The opportunity costs of a poor quality CCSS is many false negatives. Combining multiple tests may be a more cost-effective way to screen for cervical cancer in Mexico.

Use of electronic health record-based tools to improve appropriate use of the human papillomavirus test in adult women.

OBJECTIVE: To determine whether compliance with guidelines for cervical cancer screening, particularly use of the human papillomavirus (HPV) test in adult (aged ≥21 y) women, improves with the implementation of educational prompts in the electronic health record (EHR). MATERIALS AND METHODS: Two EHR-based interventions aimed at reducing unindicated HPV tests were implemented in the EHR in late June 2010. The Pap order form was revised with a descriptor next to the cotest (Pap plus HPV test) option advising that this is not for screening in women younger than 30 years, and a link to the American Society for Colposcopy and Cervical Pathology Web site was made available on the EHR home page. Charts of adult women with HPV results from January to December 2010 were reviewed. Appropriateness of HPV test ordering before (period A: from January to June) and after (period B: from July to December) the interventions were compared using the χ(2) test of association. RESULTS: A total of 3,564 HPV tests were performed on adult women at Loyola University Medical Center in 2010. During period A, 1,709 tests were ordered compared with 1,855 tests ordered during period B (p = .014). The proportion of HPV tests without an appropriate indication decreased significantly after the EHR changes (20% for period A vs 13% for period B, p < .0005). This significant decrease was seen in both primary care (22% in period A vs 12% in period B, p < .0005) and obstetrics and gynecology (Ob/Gyn) (19% vs 13%, p < .0005). CONCLUSIONS: Electronic health record-based tools improve compliance with cervical cancer screening guidelines.

A general binomial regression model to estimate standardized risk differences from binary response data.

Estimates of absolute risks and risk differences are necessary for evaluating the clinical and population impact of biomedical research findings. We have developed a linear-expit regression model (LEXPIT) to incorporate linear and nonlinear risk effects to estimate absolute risk from studies of a binary outcome. The LEXPIT is a generalization of both the binomial linear and logistic regression models. The coefficients of the LEXPIT linear terms estimate adjusted risk differences, whereas the exponentiated nonlinear terms estimate residual odds ratios. The LEXPIT could be particularly useful for epidemiological studies of risk association, where adjustment for multiple confounding variables is common. We present a constrained maximum likelihood estimation algorithm that ensures the feasibility of risk estimates of the LEXPIT model and describe procedures for defining the feasible region of the parameter space, judging convergence, and evaluating boundary cases. Simulations demonstrate that the methodology is computationally robust and yields feasible, consistent estimators. We applied the LEXPIT model to estimate the absolute 5-year risk of cervical precancer or cancer associated with different Pap and human papillomavirus test results in 167,171 women undergoing screening at Kaiser Permanente Northern California. The LEXPIT model found an increased risk due to abnormal Pap test in human papillomavirus-negative that was not detected with logistic regression. Our R package blm provides free and easy-to-use software for fitting the LEXPIT model.

[Human papillomavirus in squamous cell cancer of the head and neck. A study at the Ulm Military Hospital, Germany]. / Humane Papillomavirusinfektionen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs. Eine Untersuchung am Krankengut des Bundeswehrkrankenhauses Ulm.

There is increasing evidence worldwide that human papillomavirus is a major risk factor for head and neck cancer. Only few studies on this association have been performed in Germany to date. For the purposes of the present study, tumor specimens from 223 patients with squamous cell cancer of the oral cavity, oropharynx, hypopharynx and larynx were analyzed for HPV DNA and p16INK4a expression. The prevalence of HPV genotype 16 (HPV16) DNA in the study population was 17.5%. Further high-risk HPV types were not detected. All HPV16-positive tumors showed intense p16INK4a expression. HPV16 prevalence was highest in tonsillar carcinoma (37.5%) and lowest in laryngeal cancer (2.8%). We observed a significantly higher incidence of cervical lymph node metastases in patients with HPV16-positive tonsillar carcinoma in comparison to HPV-negative tumors (p < 0.016). Tobacco and/or alcohol consumption was significantly lower in patients with HPV-positive tumors (p < 0.0001).

Association between aerobic vaginitis, bacterial vaginosis and squamous intraepithelial lesion of low grade.

GOAL: To determine frequency of HPV infection, aerobic vaginitis and bacterial vaginosis in respondents with squamous intraepithelial lesion of lower grade comparing to respondents with normal PAP test results. MATERIAL AND METHODS: Prospective research of 100 respondents has been conducted at University-Clinic Center Tuzla and Gynecology and Obstetrics Department at Primary Health Care Center Tuzla in period from May 2011 untill January 2012. Examination program included: anamnesis, clinical gynecological examination, HPV typization, microbiological examination of vaginal and cervical smear and PAP test. RESULTS: High risk HPV group has been found more frequently among the respondents with LG SIL 46% (23) than in those with normal PAP result 14% (7) p < 0.05. Aerobic vaginitis has been found in the respondents with LG SIL in 28% (14) and there is statistically significant difference of this vaginitis comparing to the respondents with normal PAP result (p < 0.05). Bacterial vaginosis has been found in 12% (6) of the respondents with LG SIL and in 4% (2) of those with normal PAP result which is not statistically significant. In women with LG SIL and aerobic vaginitis in 9 cases E. coli has been isolated, in 4 E. faecalis and in 1 Staphylococcus aureus, while in women with normal PAP test results 3 cases of E.coli have been isolated. Examining changes in pH value of vaginal environment, higher measured values have been found in the respondents with LG SIL- 5.26 while in the respondents with normal PAP test result was 4.94 (p < 0.05). There is also statistically significant increase in the number of leukocytes in the respondents with LG SIL in relation to those with normal result. CONCLUSION: In women with LG SIL aerobic vaginitis is very common but is not an indicator of HPV infection. An adequate treatment of aerobic vaginitis would decrease the frequency of LG SIL and number of precancerous lesions which may

XPD and XRCC1 gene polymorphism in patients with normal and abnormal cervical cytology by pap smear.

AIM: The purpose of the present study was to identify the role of abnormalities in DNA repair pathways by measuring the XPD and XRCC1 gene polymorphisms. MATERIALS AND METHODS: Thirty-five patients with abnormal cervical cytology (study group) and 10 women with normal cytology (control group) were included in the study. The polymorphisms of XRCC1 Arg194Trp, XRCC1 Arg399Gln and XPD Lys751Gln genes were investigated from the blood samples. RESULTS: There was no statistically significant difference in allele frequencies of XPD gene among the groups (p = 0.097), while XRCC1R399Q gene polymorphism was strikingly more frequent in the study group than that of control cases (p = 0.029). The prevalence of XRCC1R194W gene polymorphism on the other hand, was similar between the groups (p = 0.579). CONCLUSIONS: Patients with abnormal and normal cervical cytology have similar XPD gene polymorphism. However, the frequency of gene polymorphism in XRCC1 Arg 399 Gln codon was significantly higher in abnormal cervical cytology group.

[Health technology assessment report: HPV DNA based primary screening for cervical cancer precursors]. / Health technology assessment report: ricerca del DNA di papillomavirus umano (HPV) come test primario per lo screening dei precursori del cancro del collo dell'utero.

UNLABELLED: OBJECTIVE OF THE PROJECT: The introduction of the HPV test as a primary screening test will cause important changes in the screening system based on cytology. The purposes of this report are: to define the best screening policies with HPV-based screening on the basis of the resulting efficacy and of undesired effects; comparing them to cytology-based screening; to identify their best conditions of application; to evaluate economic cost, feasibility and impact on the organisation of services of such policy in the Italian situation. CONTENTS: This report contains a section on efficacy and undesired effects based on a systematic review of literature conducted in strict coordination with the preparation of a supplement to the European Guidelines for quality assurance in cervical cancer screening. This chapter corresponds to a preliminary version of the chapter of the European Guidelines on primary screening with HPV. The sections on costs, impact on organisation, and social, ethical and legal impact reflect the Italian situation; they are based on a review of the available Italian data (including unpublished data, mainly from on-going pilot projects) and on a structured analysis of what will result if the proposed protocol is applied to the Italian situation. RESULTS: Efficacy and undesired effects. There is clear scientific evidence that a screening based on validated tests for the DNA of oncogenic HPV as primary test and applying an appropriate protocol is more effective than screening based on cytology in preventing invasive cancers of the uterine cervix. In addition, it entails a limited--if any--increase of the undesired effects both in terms of unneeded referral to diagnostic work-up and in terms of over-diagnosis and consequent overtreatment of spontaneously regressive lesions. The crucial elements of such protocol are the followings: HPV-positive women are not to be directly referred to colposcopy, but the use of triage systems is essential. The currently recommendable method is based on performing cytology in HPV positive women. If the result of this test is abnormal, the woman is immediately referred to colposcopy; if cytology is normal, the woman is invited to repeat a new HPV test after one year. In case such a test is still positive, the woman is referred to colposcopy; in case of negative result, the woman will be re-invited for a new screening round at the regular interval. In organised population-based screening programmes the interval after a negative primary HPV test should be at least 5 years. There is evidence that the 5-year cumulative risk of high-grade CIN after a negative HPV test is lower than the 3-year risk after a normal cytology. On the other hand, the probability of unneeded colposcopies and treatments would plausibly be relevant with 3-year intervals after a negative HPV test. HPV-based screening should not start before 30-35 years. There is evidence that below 30 years HPV-based screening leads to an increased overdiagnosis of CIN2 that would regress spontaneously, with consequent overtreatment. Some increase in overdiagnosis is plausible also between 30 and 34 years. Below such ages, cytological screening is the recommended test. Only tests for the DNA of oncogenic HPV, validated according to the European guidelines as for sensitivity and specificity for high-grade lesions, should be applied. There is no evidence that double testing with cytology and HPV is more protective than stand-alone HPV as primary test, although it entails a small and not relevant increase in sensitivity vs stand-alone HPV. On the contrary, there is evidence that double testing causes a substantial increase in referral to colposcopy and a decrease in its PPV. For this reason, if HPV is used as primary screening test, it is recommended not to add cytology in parallel. Cost and economic evaluation. It is estimated that, if the protocol described is applied, in the current Italian situation the overall costs of HPV-based screening are lower than those of conventional cytological screening applied at the current 3-year intervals, although the cost of each screening round is higher. Impact on organization. For reasons of quality and cost, both the interpretation of cytology and HPV testing require a centralisation. This need is particularly strong, in terms of costs, for HPV test execution. It is therefore recommended to perform the HPV test in a limited number of reference laboratories of large size. This also makes monitoring and evaluating the spontaneous activity easier. HPV-based screening entails problems of organisation related to the need of triage, to complex protocols and to reconversion of the activities of cytological interpretation. Social, ethical and legal impact. The communication of the result of the HPV test to women, particularly if positive, is a further crucial aspect in order to reduce not only the emotional impact, but also the possible risks that women are inappropriately managed or lost to follow-up. Great efforts must be put in the education of healthcare professionals, both directly involved in organised programmes or not, particularly private gynaecologists and general practitioners. RECOMMENDATIONS: In conclusion, the crucial requirement to introduce HPV-based screening programmes is the capacity to guarantee the application of appropriate screening protocols. If protocols do not respect the criteria described above they can cause relevant increase of undesired effects and costs compared to cytology-based screening. Therefore they should be avoided, except in studies able to provide clear evidence about human and economic costs. For this purpose, correct education and information both to healthcare professionals and to the population is needed. In the Italian situation, where organised screening and a relevant spontaneous activity coexist, their interaction is crucial. Actions directed to integrate them and to guarantee as more uniformity of interventions as possible are needed, in particular through the integration of registries and thorough monitoring and a progressive homogenization of protocols. In order to grant the safety of transition, it is needed that the HPV-based organised screening activities are strictly monitored and that the National Centre for Screening Monitoring (ONS) ensures coordination. Knowledge about HPV based screening is still rapidly evolving. It is possible that currently on-going researches suggest changes to the optimal protocols in the next few years, particularly as for the management of HPV positive women. In addition, studies on the validation of new assays were recently published and others are expected. It is suggested to exploit the organised screening activity to produce scientific evidence, in order to clarify the still uncertain aspects of optimal protocols. Different protocols in terms of screening intervals, age of application and management of HPV positive women should be studied in the frame of controlled implementation, through multicentre projects coordinated by ONS. Finally, it is suggested the creation of a National working group to promptly update the recommendations for screening and the list of assays to be considered as validated. On the bases of the results obtained in the first vaccinated cohorts reaching the screening age, for the future, it will be crucial to deliver specific recommendations to the population vaccinated against HPV during adolescence.