Cervical Intraepithelial Neoplasia 3 (Cervical Intraepithelial Neoplasia 3/High-Grade Squamous Intraepithelial Lesion) in Human Papillomavirus-Vaccinated Women-Results From a Tertiary Referral Center.

OBJECTIVE: High-grade cervical intraepithelial neoplasia (CIN 3) still develops in some vaccinated women despite established effectiveness of prophylactic human papillomavirus (HPV) vaccination. The purpose of this study was to define characteristics of women with CIN 3 after HPV vaccination referred to a gynecological dysplasia unit. MATERIALS AND METHODS: Retrospective analysis of HPV-vaccinated women with CIN 3 in a single German center. Between July 2018 and September 2020, 791 women were referred to our university hospital-based dysplasia unit for colposcopic evaluation of abnormal cytological findings. Human papillomavirus vaccination status was retrieved. Human papillomavirus typing was performed in lesional biopsies and cervical swabs. RESULTS: Nine women were identified who had previously been vaccinated with the quadrivalent HPV vaccine (Q-HPV) and were diagnosed with histologically confirmed CIN 3/high-grade squamous intraepithelial lesion. The Q-HPV had been administered between 12 and 28 years of age and 1-13 years before CIN 3 diagnosis. Nine different high-risk (HR)-HPV types were found in the CIN 3 biopsies, 6 monoinfections (twice HPV 16, once HPV 18, HPV 31, HPV 52, HPV 58, respectively) and 3 dual infections (HPV 33 + 52, HPV 51 + 52, HPV 53 + 66). Seven of these 9 HR-HPV types are not covered by Q-HPV, but only 2 CIN 3 lesions carried HR-HPV types not included in the nonavalent HPV vaccine. CONCLUSIONS: It is important to implement vaccination recommendations and administer HPV vaccination as early as possible in HPV-naive individuals. Because not all HR-HPV types are covered by the available HPV vaccines, other types may still cause CIN 3/high-grade squamous intraepithelial lesion. This requires further screening after vaccination, especially in women who were previously vaccinated with the bivalent or the quadrivalent HPV vaccine.

Cervical Cancer Screening: Comparison of Conventional Pap Smear Test, Liquid-Based Cytology, and Human Papillomavirus Testing as Stand-alone or Cotesting Strategies.

BACKGROUND: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study. METHODS: The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias), and potential harms, including number of colposcopies needed to detect 1 precancerous lesion (NNC), were calculated. RESULTS: In 2,627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting: 99%; PCR cotesting: 84%), but at the cost of lower specificities (92%-95%) compared with HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2: 1.06, 95% confidence interval (CI), 1.00-1.21; PCR: 1.07, 95% CI, 1.00-1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests: 0.99, 95% CI, 0.99-1.00). NNC was highest for Pap cotesting. CONCLUSIONS: Cotesting offers no benefit in detection over stand-alone HPV testing, resulting in more false positive results and colposcopy referrals. IMPACT: HPV stand-alone screening offers a better balance of benefits and harms than cotesting.See related commentary by Wentzensen and Clarke, p. 432.

A successful multidisciplinary approach for treatment and for preserving the reproductive potential in a rare case of acute lymphocytic leukemia during pregnancy.

Leukemia in pregnancy is a rare condition with the prevalence of 1 in 75,000-100,000 pregnancies. In this case report, we present a successful multidisciplinary management strategy for treatment and for preserving the reproductive potential in a rare case of acute lymphocytic leukemia (ALL) during pregnancy. Several complex challenges existed and necessitated a multidisciplinary approach with strong coordination and collaboration between oncologists, gynecologists, reproductive cryobiologists, obstetricians, and neonatologists in order to improve the maternal and fetal outcome. Pregnancy in the second trimester is neither a contraindication for ALL treatment nor for emergency fertility preservation via ovarian tissue extraction and further cryopreservation.

Cervical screening program and the psychological impact of an abnormal Pap smear: a self-assessment questionnaire study of 590 patients.

PURPOSE: Invasive cervical cancer is today the fourth most common cancer of women in western civilization. Screening programs have led to a continuously decrease. Nevertheless, both screening and a positive test result are known to be associated with a negative psychological impact. Screening programs in European countries differ and thus psychological impact might as well. The aim of this study was to evaluate the psychological impact of women with an abnormal Pap smear in a German cohort. METHODS: Between July 2013 and May 2014, a self-assessment questionnaire was distributed to 595 patients that were referred to a special clinic for cervical dysplasia for further evaluation of an abnormal Pap smear. Patients were recruited in five different centers. RESULTS: Most patients (45.9 %) were informed about the test result via phone call by their doctor. 68.8 % of the patients felt anxious and 26.3 % even felt panic. After having talked to their physician, 51.4 % of our cohort still felt worried and only 24.4 % felt reassured. Concerning disease management, 48.4 % underwent a control Pap smear in 6 months. The preferred information source was the physician (63.9 %). Compared to the results in other European countries, our study cohort showed differences concerning age distribution, patients living in a partnership, number of children and especially disease management. CONCLUSION: Cancer screening itself and abnormal test results have an impact on patient's feelings. To reduce the psychological impact, patients need to be better informed about the risks and benefits of cancer screening programs and in case of cervical cancer screening about the meaning of an abnormal test result. Our results underline the importance of a trustful physician-patient relationship in that matter.

The number of removed lymph nodes by inguinofemoral lymphadenectomy: impact on recurrence rates in patients with vulva carcinoma.

OBJECTIVE: Inguinal lymph node (LN) metastasis is a crucial prognostic factor in vulva carcinoma. The aim of this study was to determine the prognostic value of the number of resected LNs in patients with vulvar carcinoma on recurrence rates. METHODS: This retrospective study includes patients with vulvar squamous cell carcinoma who underwent inguinofemoral lymphadenectomy (IFL) between 1998 and 2011. Dissected groins were stratified by the number of removed lymph nodes (<6 LNs versus ≥6 LNs) or inguinal LN metastasis (pN- versus pN+) and analyzed according to groin, local and distance recurrence rates. RESULTS: In total 45 patients were identified and 79 groins were eligible for this analysis. 11 patients underwent ipsilateral IFL and 34 bilateral IFL. The median age was 58 years (range 31-80). The median tumor size was 2 cm (range 0.1-7.9). A median of 8 (range 0-19) LNs were resected per groin. Overall in 11 groins LN metastases were found. Groin recurrences occurred in four patients, local recurrence in six patients and distant metastasis in one patient. We did not observe any significant improvement in groin recurrence rates, local recurrence rates and distant recurrence rates if more than six LNs were removed per groin. Notably, patients with LN metastasis did not show higher recurrence rates compared to unaffected LNs. CONCLUSION: In this cohort we demonstrated that resection of more than six LNs per groin does not improve the recurrence rates in patients with carcinoma of the vulva. Further prospective studies with more individuals are needed to evaluate the role of resected LNs in vulvar carcinoma.