Impact of knowledge of human papillomavirus positivity on cervical cytology performance in Latin America

Corresponding author: Arianis Tatiana Ramírez, Early Detection, Prevention & Infections Branch, International Agency for Research on Cancer, 25 avenue Tony Garnier, 69007 Lyon, France ([email protected]).Background: Cervical cytology is recommended by the World Health Organization as a triage option in human papillomavirus (HPV)- based cervical cancer screening programs. We assessed the performance of cytology to detect CIN3þ without and with knowledge of HPV positivity. Methods: Women were screened with cytology and HPV across ESTAMPA study centers in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were reinterpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3þ without and with knowledge of HPV positivity were estimated. Findings: A total of 4087 women were included, of which 490 had histologically confirmed CIN3þ (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3þ was 47.2% (95% CI ¼ 42.5 to 51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI ¼ 54.2 to 63.5; P<.0001). The specificity without knowledge of HPV was 89.4% (95% CI ¼ 88.2 to 90.5), whereas with knowledge of HPV positivity was 78.9% (95% CI ¼ 77.4 to 80.4; P<.0001). Performance estimates varied by study center for cytology without knowing the HPV positivity (range ¼ 32.8%-61.5% for sensitivity; range ¼ 80.7%-98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1%-93.4% for sensitivity; 39.6%-98.6% for specificity). Conclusion: The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals.Consejo Nacional de Ciencia y TecnologíaPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Proyectos de investigación y desarroll

Genital infections in high-risk human papillomavirus positive Paraguayan women aged 30-64 with and without cervical lesions.

ObjectiveTo determine the prevalence of genital infections (GIs), including sexual transmitted STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and opportunistic pathogens that generally do not cause STIs, non-classic STI: Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma hominis, in women with high-risk oncogenic human papillomavirus (hr-HPV) infection and their association with cervical lesions.MethodsA cross-sectional study was carried out including 231 hr-HPV positive women. Of these, 46 has histologically confirmed cervical intraepithelial neoplasia 3 (CIN3) or more (including CIN3 and cervical cancer lesions-CIN3+). GIs were detected by multiplex real time PCR. Odds ratios (OR) were estimated to explore possible associations between GIs and the presence or absence of CIN3+ lesions. Additionally, we examined associations between sociodemographic, sexual, and clinical characteristics and the presence of GIs.ResultsIn total, there were 174/231 cases of GIs corresponding to an overall prevalence of 75.3% (95%CI: 69.4-80.4), being non-classic STIs the most common (72.3%) compared to STIs (12.6%). The most prevalent non-classic STI and STI were U. parvum (49.8%) and C. trachomatis (7.4%), respectively. The odds of presenting GIs were 3 times higher in women under 46 years compared to older counterparts (OR: 3.32, 95%CI: 1.74-6.16), and in women with a normal Pap smear with inflammation compared to those without inflammation (OR: 3.31, 95%CI: 1.15-9.77). GIs were equally present in women with and without CIN3+ lesions.ConclusionWe observed an association of GIs with inflammation in the Pap smear, but no association with CIN3+, as some of them are very common and likely part of the normal vaginal flora, suggesting that such infections do not appear to be cofactors in cervical carcinogenesis, although larger prospective studies are needed

Factors associated with high-risk human papillomavirus infection and high-grade cervical neoplasia: A population-based study in Paraguay.

BACKGROUND:Cervical cancer (CC) is one of the leading causes of cancer mortality among women from Paraguay, with high incidence and mortality rates (31.2 and 16 per 100 000 women, respectively). Although the risk factors associated with high-risk human papillomavirus (hrHPV) infection and preneoplastic cervical lesions are widely studied, population-based characteristics of particular settings may influence the feasibility of HPV-based CC screening implementation. This study aimed to explore factors associated with hrHPV infection and high-grade cervical neoplasia in hrHPV-positive (hrHPV+) women from Paraguay. METHODS:A total of 5677 women aged 30-64 years from the Central Department of Paraguay were screened with HPV test (Hybrid Capture 2) and Pap smear. Sociodemographic and risk factor interviews were conducted. hrHPV+ women were referred to colposcopy and women with an abnormal colposcopy had a biopsy taken. The outcomes recorded were the hrHPV status and the presence of high-grade cervical intraepithelial neoplasia or worse (CIN2+) among hrHPV+ women. Associations were investigated using multivariate logistic regressions. RESULTS:hrHPV prevalence was 13.8% (95%CI 13.0-14.8). This value decreased with the age of women (p-trend<0.001) and increased with the lifetime number of sexual partners (p-trend<0.001) and number of previous female partners of their current male partner if women had had one lifetime sexual partner (p-trend<0.001), increasing from 3.06 (95%CI 0.073-20.9) if partners had had one previous female partner to 9.19 (95%CI 2.36-61.1) if they had had eight or more. In hrHPV+ women, CIN2+ prevalence was 10.7% (95%CI 8.58-13.2) and increased with time since the last Pap smear (p-trend<0.001) and with the increasing number of pregnancies (p-trend = 0.05). CONCLUSION:In these settings, the sexual behavior of women and their male partners is associated with hrHPV infection. In hrHPV+ women, underscreening practices and multiple pregnancies are associated with CIN2+. This knowledge can contribute to public health policies for CC prevention and control in Paraguay