European consensus statement on expert colposcopy.

BACKGROUND: Following the publication of the European consensus statement on standards for essential colposcopy in 2020, the need for standards relating to more complex and challenging colposcopy practice was recognised. These standards relate to colposcopy undertaken in patients identified through cervical screening and tertiary referrals from colposcopists who undertake standard colposcopy only. This set of recommendations provides a review of the current literature and agreement on care for recognised complex cases. With good uptake of human papillomavirus (HPV) immunisation, we anticipate a marked reduction in cervical disease over the next decade. Still, the expert colposcopist will continue to be vital in managing complex cases, including previous cervical intraepithelial neoplasia (CIN)/complex screening histories and multi-zonal disease. AIMS: To provide expert guidance on complex colposcopy cases through published evidence and expert consensus. MATERIAL & METHODS: Members of the EFC and ESGO formed a working group to identify topics considered to be the remit of the expert rather than the standard colposcopy service. These were presented at the EFC satellite meeting, Helsinki 2021, for broader discussion and finalisation of the topics. RESULTS & DISCUSSION: The agreed standards included colposcopy in pregnancy and post-menopause, investigation and management of glandular abnormalities, persistent high-risk HPV+ with normal/low-grade cytology, colposcopy management of type 3 transformation zones (TZ), high-grade cytology and normal colposcopy, colposcopy adjuncts, follow-up after treatment with CIN next to TZ margins and follow-up after treatment with CIN with persistent HPV+, and more. These standards are under review to create a final paper of consensus standards for dissemination to all EFC and ESGO members.

Assessing cervical intraepithelial neoplasia as an indicator disease for HIV in a low endemic setting: a population-based register study.

OBJECTIVES: To analyse whether the prevalence of undiagnosed HIV among (1) all women in Sweden and (2) migrant women, diagnosed with cervical intraepithelial neoplasia grade 2 or worse CIN2+ reaches the threshold of 0.1%, which has been suggested to be cost-effective for HIV testing. DESIGN: Population-based register study. SETTING: Counties of Stockholm and Gothenburg, Sweden, 1990-2014. POPULATION: All women, born between 1940 and 1990, with at least one cervical cytology or histology registered in the Swedish National Cervical Screening Register (NKCx). METHODS: Data were collected from the NKCx and the Swedish National HIV register. The proportion of women with undiagnosed HIV among women with CIN2+ compared with women with a normal/mildly abnormal cytology/histology was assessed. MAIN OUTCOME MEASURES: Proportion of women with undiagnosed HIV. RESULTS: The proportion of undiagnosed HIV was higher among all women with CIN2+ than among those without CIN2+ : 0.06% (95% CI 0.04-0.08) versus 0.04% (95% CI 0.04-0.04); P = 0.017). Among migrant women, the proportion of undiagnosed HIV was higher among those with CIN2+ than among those without [0.30% (95% CI 0.20-0.43) versus 0.08% (95% CI 0.07-0.10); P < 0.001] and exceeded 0.1%, suggesting the cost-effectiveness of HIV testing. Women with undiagnosed HIV at the time of CIN2+ had a significantly lower nadir CD4+ T-cell count, as a measure of immunosuppression, compared with women without CIN2+ before HIV diagnosis (median nadir CD4, 95 cells/mm3 versus 210 cells/mm3 ; P < 0.01). CONCLUSIONS: HIV testing should be performed in migrant women with unknown HIV status diagnosed with CIN2+ . TWEETABLE ABSTRACT: HIV testing should be performed in migrant women with unknown HIV status diagnosed with CIN2+ .

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up.

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

Chlamydia trachomatis PCR (Cobas Amplicor) in women: endocervical specimen transported in a specimen of urine versus endocervical and urethral specimens in 2-SP medium versus urine specimen only.

The sensitivity of Roche Cobas Amplicor Chlamydia trachomatis polymerase chain reaction (PCR) including the internal control (IC) programme to identify inhibition, was investigated on 3 different samples from women: (1) swab samples from the urethra and the cervix pooled in 2-SP transport medium, (2) swab sample from the cervix transported in a urine sample from the same patient, and (3) urine sample alone. Out of the 2412 patients, 193 (8.0%) were chlamydia positive and in 14 of these the results showed discrepancies between sampling methods. The sensitivity of PCR on urethra/cervix, urine/cervix and urine was 98.4% (190/193), 97.9% (189/193) and 93.3% (180/193) respectively. The higher sensitivity of PCR on urethra/cervix and urine/cervix as compared with urine alone was statistically significant. Without the IC, the sensitivity of PCR on urethra/ cervix, urine/cervix and urine would have been 95.9% (185/193), 94.8% (183/193) and 90.7% (175/193) respectively. Factors influencing the rate of inhibition were also studied.

A population-based five-year follow-up study of cervical human papillomavirus infection.

OBJECTIVE: The purpose of this study was to determine the long-term tendency for cervical human papillomavirus infections to persist in the general population. STUDY DESIGN: From 500 women who participated in a 1991 population-based survey, 90 healthy women with normal results of cytologic examination (women with human papillomavirus deoxyribonucleic acid detected and age-matched control women without human papillomavirus deoxyribonucleic acid detected) were interviewed and examined 5 years later colposcopically, cytologically, and with human papillomavirus serologic testing and human papillomavirus deoxyribonucleic acid testing by polymerase chain reaction with 2 different consensus primer pairs (MY09 and MY11 and GP5(+) and GP6(+)), type-specific polymerase chain reaction, and deoxyribonucleic acid sequencing. RESULTS: The 5-year human papillomavirus clearance rate was 92%. Only human papillomavirus type 16 infections persisted. Colposcopic impression of grade 2 cervical intraepithelial neoplasia was associated with persistent human papillomavirus 16 infection (P <.03). Human papillomavirus detection was associated with sexual history. Human papillomavirus type was the only determinant of human papillomavirus persistence. CONCLUSION: The high clearance rates in a population-based setting with a 5-year follow-up period imply that inclusion of human papillomavirus deoxyribonucleic acid testing in population-based cervical screening programs should target persistent infection.

Conization for cervical intraepithelial neoplasia is followed by disappearance of human papillomavirus deoxyribonucleic acid and a decline in serum and cervical mucus antibodies against human papillomavirus antigens.

OBJECTIVE: Our purpose was to investigate whether conization for cervical intraepithelial neoplasia eliminates human papillomavirus deoxyribonucleic acid and effects the levels of serum and cervical mucus antibodies against human papillomavirus antigens. STUDY DESIGN: Analysis of paired cervical brush and serum samples taken from 23 women with cervical intraepithelial neoplasia before and 16 to 27 months after conization was performed for presence of human papillomavirus deoxyribonucleic acid by polymerase chain reaction and for human papillomavirus antibodies by enzyme-linked immunosorbent assay. RESULTS: Four women had recurrent cervical intraepithelial neoplasia, whereas 19 women were disease free. Eighteen of 23 women were positive for human papillomavirus deoxyribonucleic acid before treatment. At follow-up only the 4 women with recurrent cervical intraepithelial neoplasia were positive. Serum immunoglobulin G levels and A levels and immunoglobulin A levels in cervical mucus against most of the tested human papillomavirus antigens had declined at follow-up. CONCLUSIONS: Human papillomavirus deoxyribonucleic acid was regularly eliminated and human papillomavirus antibody levels, especially local immunoglobulin A, declined after efficient treatment, suggesting that conization may be effective for treating the underlying human papillomavirus infection.

Serological responses to human papillomavirus type 16 antigens in women before and after renal transplantation.

Female renal transplant recipients have an increased incidence of human papillomavirus (HPV) associated lesions, such as cervical dysplasia and neoplasia [Schneider et al., 1983]. In this study we tested the serological responses by enzyme-linked immunoadsorbent assays (ELISA) to 3 different antigenic regions of HPV type 16. Sera from 35 female renal transplant patients collected before and at different times, up to 3 years, after transplantation were collected and tested. Before transplantation IgG antibodies against peptide 49, corresponding to the HPV L2 region, were found in 21/35 of the patients' sera. Of the L2 positive sera, 16 also demonstrated activity with the HPV L1 region derived peptide 31. All sera that were active against peptide 31 (L1) were also reactive with peptide 49 (L2). After renal transplantation, the antibody levels against these 2 peptides (peptides 49 and 31) dropped significantly (OD > or = 0.2) in all previously positive sera and remained so throughout the study, which lasted up to 3 years. The proportion of patients with IgA activity against the E2 region (peptide 245), which is common among patients with cervical neoplasia, increased from 9/35 before transplantation to 18/35 after transplantation. In parallel, we monitored 25 of these patients' sera before and after transplantation for antibody activity against measles, adenoviruses, and cytomegaloviruses (CMV). The majority of these sera--17/25 (68%) and 18/25 (72%), respectively--had no titer changes against measles and adenoviruses. Furthermore, the changes in antibody titers observed with CMV in these patients were not correlated with the fate of the antibodies against the HPV peptides.(ABSTRACT TRUNCATED AT 250 WORDS)