Abnormal Cytology Research Articles

Novel Strategy for the Management of Cervical Multicystic Diseases

PurposeTo investigate the clinical practices of diagnosing multicystic cervical lesions as a means to develop a more appropriate diagnostic algorithm for gastric-type adenocarcinoma (GAS) and its precursors.MethodsClinical information for 159 surgically treated patients for multicystic disease of the uterine cervix was collected from 15 hospitals. We performed a central review of the MRI and pathological findings. The MRI findings were categorized into four types including two newly proposed imaging features based on the morphology and distribution of cysts, and the diagnosis accuracy was assessed. Among the four MRI types, types 1 and 2 were categorized as benign lesions that included LEGH; type 3 were precancerous lesions (with an assumption of atypical LEGH); and type 4 were malignant lesions.ResultsThe central pathological review identified 56 cases of LEGH, seven with GAS, four with another form of carcinoma, and 92 with benign disease. In clinical practice, over-diagnosis of malignancy (suspicion of MDA) occurred for 12/19 cases (63.2%) and under-diagnosis of malignancy occurred for 4/11 (36%). Among the 118 patients who had a preoperative MRI and underwent a hysterectomy, type 3 or 4 MRI findings in conjunction with abnormal cytology were positively indicative of premalignancy or malignancy, with a sensitivity and specificity of 61.1% and 96.7%, respectively.ConclusionsAlthough the correct preoperative diagnosis of cervical cancer with a multicystic lesion is challenging, the combination of cytology and MRI findings creates a more appropriate diagnostic algorithm that significantly improves the diagnostic accuracy for differentiating benign disease from premalignancy and malignancy.

Efficacy of optical coherence tomography in the triage of women with minor abnormal cervical cytology before colposcopy.

To evaluate the efficacy of Optical Coherence Tomography (OCT) for detecting cervical lesions in women with minor abnormal cytology results (atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL)). A prospective study was conducted at gynecologic clinic from Mar 2021 to Sep 2021. The recruited women with cervical cytological findings of ASC-US or LSIL were inspected with OCT before colposcopy-directed cervical biopsy. The diagnostic performance of OCT, alone and in combination with high-risk human papillomavirus (hrHPV) testing were evaluated to detect cervical intraepithelial neoplasia of grade 2 or worse (CIN2+)/CIN3 or worse (CIN3+). The rate of colposcopy referral and the immediate risk of CIN3+ of OCT were calculated. A total of 349 women with minor abnormal cervical cytology results were enrolled. For detection of CIN2+/CIN3+, the sensitivity and NPV of OCT were lower than those of hrHPV testing (CIN2+: 71.3% vs. 95.4%, 89.0% vs. 91.1%, P < 0.001; CIN3+: 75% vs. 93.8%, 96.5% vs. 95.6%, P < 0.001), but the specificity, accuracy and PPV were higher than those of hrHPV testing (CIN2+: 77.5% vs. 15.6%, 75.9% vs. 35.5%, 51.2% vs. 27.3%, P < 0.001; CIN3+: 69.4% vs. 13.6%, 69.9% vs. 20.9%, 19.8% vs. 9.9%, P < 0.001). OCT combined with hrHPV testing (CIN2+: 80.9%; CIN3+: 72.6%) showed higher specificity than that of OCT alone (P < 0.001). The colposcopy referral rate base on OCT classification was lower than that based on hrHPV testing (34.7% vs. 87.1%, P < 0.001). Patients with hrHPV-positive ASC-US and hrHPV-negative LSIL cytology, the immediate CIN3+ risk in OCT negative cases was less than 4%. OCT alone or combination with hrHPV testing shows good performance for detecting CIN2+/CIN3+ in patients with ASC-US/LSIL cytology. OCT is an effective method for colposcopy triage in women with hrHPV-positive ASC-US and hrHPV-negative LSIL cytology.

HPV-induced host epigenetic reprogramming is lost upon progression to high-grade cervical intraepithelial neoplasia.

The impact of a pathogen on host disease can only be studied in samples covering the entire spectrum of pathogenesis. Persistent oncogenic human papilloma virus (HPV) infection is the most common cause for cervical cancer. Here, we investigate HPV-induced host epigenome-wide changes prior to development of cytological abnormalities. Using cervical sample methylation array data from disease-free women with or without an oncogenic HPV infection, we develop the WID (Women's cancer risk identification)-HPV, a signature reflective of changes in the healthy host epigenome related to high-risk HPV strains (AUC=0.78, 95% CI: 0.72-0.85, in nondiseased women). Looking at HPV-associated changes across disease development, HPV-infected women with minor cytological alterations (cervical intraepithelial neoplasia grade 1/2, CIN1/2), but surprisingly not those with precancerous changes or invasive cervical cancer (CIN3+), show an increased WID-HPV index, indicating the WID-HPV may reflect a successful viral clearance response absent in progression to cancer. Further investigation revealed the WID-HPV is positively associated with apoptosis (ρ=0.48; P < .001) and negatively associated with epigenetic replicative age (ρ=-0.43; P < .001). Taken together, our data suggest the WID-HPV captures a clearance response associated with apoptosis of HPV-infected cells. This response may be dampened or lost with increased underlying replicative age of infected cells, resulting in progression to cancer.

Evaluation of 1,030,482 Cervical Smear Results in Brazilian Population.

The objective was to determine the prevalence of abnormal cytologic smears in a large population of a Brazilian city. Retrospective study of cervical cytology results performed at a private laboratory in São Paulo - Brazil. A total of 1,030,482 cytology tests were performed between January 2010 and December 2015. Among the satisfactory cytologies, we observed abnormal results in 8.9% (91,371). Analyzing the proportion of exams with altered results over the years, there was no change in these rates. We observed that the proportion of abnormal exams decreased with increasing age. Atypical squamous cells of undetermined significance, possibly non-neoplastic (ASC-US) cytology was the most common abnormality found in the general population with 73.19%, followed by low-grade intraepithelial lesion (LSIL) with 20.5%; these 2 cytological abnormalities add up to 93.69 % of all abnormal results. There was an increase in ASC-US with advancing age, a decrease in prevalence of LSIL, especially after the age of 30 and high-grade intraepithelial lesion (HSIL) shows two peaks of elevation, respectively in the age groups of 30-39 years and over 70 years. Women under the age of 30 showed a higher prevalence of cytological abnormalities, however most of these changes are low-grade lesions. In older women, cytological abnormalities are largely high-grade lesions, requiring greater care to prevent progression to cancer.

ICOS/ICOSLG and PD-1 Co-Expression is Associated with the Progression of Colorectal Precancerous- Carcinoma Immune Microenvironment.

This study aimed to investigate the expression of inducible T-cell co-stimulator (ICOS) and its ligand (ICOSLG), along with their association with clinicopathological features and influence on the immune profile in colorectal cancer (CRC). The Cancer Genome Atlas Colorectal Adenocarcinoma cohorts were used. We also analyzed 131 clinical samples of colon lesions, including precancerous lesions (hyperplastic polyps, low-grade dysplasia, and high-grade dysplasia) and CRC tissues. We conducted immunohistochemical (IHC) assays and multiple IHC (mIHC) of CD4+, Foxp3+ tumor-infiltrating lymphocytes (TILs), and PD-1/PD-L1 immune checkpoints in precancerous lesions and CRC samples from our patient subsets to determine changes and correlations in ICOS and ICOSLG expression during progression through the adenoma-carcinoma pathway. High expression of ICOS and ICOSLG was a significant factor in CRC in multiple analyses and was positively correlated with CD4+/Foxp3+ TIL density and PD-1/PD-L1 expression, which increased with the sequential progression of lesions from precancerous tissues to carcinoma. Multivariable logistic regression analysis suggested that the location and expression level of ICOS/ICOSLG may be involved in precancerous-carcinoma progression. The co-expression status of PD-1 and ICOS/ ICOSLG could stratify patients with colorectal lesions into three groups of low, moderate, and high risk of progression. According to this classification and mIHC assays, we found a strong correlation between increased PD-1+ICOS+ or PD-1+ICOSLG+ co-expression and CRC, which might be deemed an independent factor in carcinogenesis. Increased ICOS/ICOSLG expression may be associated with the progressive formation of Foxp3+ TILs in the immune microenvironment and may further promote the development of the abnormal cytology of colorectal lesions from precancerous neoplasia to CRC. Our findings support the interpretation that enhanced co-expression of PD-1+ICOS+ or PD-1+ICOSLG+ contributes to the immune-active microenvironment of the colorectal adenoma-carcinoma sequence.

Endocervical Sampling in Women With Suspected Cervical Neoplasia: A Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies

ABSTRACT HPV-induced cervical neoplasia progresses through a predictable natural course of disease, starting with mild cervical intraepithelial neoplasia (CIN1) and developing into severe degrees (CIN3) and eventually to invasive cervical cancer. A positive finding on initial screening for cervical neoplasia results in further diagnostics involving sampling with an endocervical brush (EB) or endocervical curettage (ECC). There exists a considerable variation in the choice of test method for obtaining these endocervical or cervical canal samples. This meta-analysis aimed to retrospectively determine the diagnostic test accuracy (DTA) and patient discomfort of the EB and ECC for the detection of cervical neoplasia in women with any indication for colposcopy, biopsies, and endocervical sampling. All diagnostic studies and randomized clinical trials that included women with abnormal cytology results in cervical cancer screening or women with red flag symptoms undergoing colposcopy, biopsy, EB, or ECC were included. The target condition was cervical neoplasia, and the reference standard was the final histological result. A bivariate random-effects model was used to determine summary estimates of sensitivity and specificity with 95% confidence intervals (CIs). A meta-analysis assessing summary relative risk for inadequate samples was also conducted. A total of 7 studies were included in the meta-analysis with a total sample size of 1097 women. Three studies were randomized clinical trials, and 4 were cohort studies, and they took place between 1988 and 2013. A DTA meta-analysis for summary sensitivity and specificity found an overall pooled sensitivity of 81% (95% CI, 48–95) for EB and 70% (95% CI, 42–89) for ECC. The overall pooled specificity was 73% (95% CI, 36–93) for EB and 81% (95% CI, 56–94). The overall relative risk was found to be 2.53 (95% CI, 0.58–11.0; P = 0.215) for ECC compared with EB for inadequate samples. Two studies reported patient discomfort as an outcome, and only a single study reported a significant difference between ECC and EB in favor of ECC (visual analog scale score 2.55 vs 1.99). The results of this meta-analysis comparing the DTA of EB and ECC found no significant difference between EB and ECC in DTA, inadequate sampling rate, or adverse effects. The overall sensitivity was found to be slightly higher for EB than for ECC and the specificity to be slightly higher for ECC than EB, although these results were not statistically significant.

13-Type HPV DNA Test versus 5-Type HPV mRNA Test in Triage of Women Aged 25-33 Years with Minor Cytological Abnormalities-6 Years of Follow-Up.

A specific, cost-effective triage test for minor cytological abnormalities is essential for cervical cancer screening among younger women to reduce overmanagement and unnecessary healthcare utilization. We compared the triage performance of one 13-type human papillomavirus (HPV) DNA test and one 5-type HPV mRNA test. We included 4115 women aged 25-33 years with a screening result of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) recorded in the Norwegian Cancer Registry during 2005-2010. According to Norwegian guidelines, these women went to triage (HPV testing and repeat cytology: 2556 were tested with the Hybrid Capture 2 HPV DNA test, which detects the HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68; and 1559 were tested with the PreTect HPV-Proofer HPV mRNA test, which detects HPV types 16, 18, 31, 33, and 45). Women were followed through December 2013. HPV positivity rates at triage were 52.8% and 23.3% among DNA- and mRNA-tested women (p < 0.001), respectively. Referral rates for colposcopy and biopsy and repeat testing (HPV + cytology) after triage were significantly higher among DNA-tested (24.9% and 27.9%) compared to mRNA-tested women (18.3% and 5.1%), as were cervical intraepithelial neoplasia grade 3 or worse (CIN3+) detection rates (13.1% vs. 8.3%; p < 0.001). Ten cancer cases were diagnosed during follow-up; eight were in DNA-tested women. We observed significantly higher referral rates and CIN3+ detection rates in young women with ASC-US/LSIL when the HPV DNA test was used at triage. The mRNA test was as functional in cancer prevention, with considerably less healthcare utilization.

The Impact of HPV Diagnosis and Abnormal Cervical Cytology Results on Sexual Dysfunction and Anxiety.

The objective of this study is to evaluate the effect of HPV diagnosis on the sexual function and anxiety levels of Turkish women. A total of 274 female patients who tested positive with HPV were included in the study and categorized into four groups: Group 1 (HPV 16/18 with normal cytology), Group 2 (HPV 16/18 with abnormal cytology), Group 3 (other high-strain HPV with normal cytology), and Group 4 (other high-strain HPV with abnormal cytology). All patients filled out the Beck Anxiety Inventory (BAI) and Female Sexual Function Index (FSFI) at the time when they tested positive for HPV and during the two-month and six-month follow-ups. Significant increases were observed in BAI scores in all four groups, whereas significant decreases were observed in total FSFI scores in Groups 1 and 2 only(p < 0.05). BAI scores of Groups 1 and 2 were significantly higher than those of Groups 3 and 4 (p < 0.05). FSFI scores of Groups 1 and 2 measured during the sixth-month follow-up were significantly decreased (p = 0.004 and p < 0.001, respectively). Our findings suggest that patients with HPV 16 and 18 positivity and abnormal cytological findings are more likely to have high anxiety and sexual dysfunction.

Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus: results from the ESTAMPA multicentric screening study

Colposcopy, currently included in WHO recommendations as an option to triage human papillomavirus (HPV)-positive women, remains as the reference standard to guide both biopsy for confirmation of cervical precancer and cancer and treatment approaches. We aim to evaluate the performance of colposcopy to detect cervical precancer and cancer for triage in HPV-positive women. This cross-sectional, multicentric screening study was conducted at 12 centres (including primary and secondary care centres, hospitals, laboratories, and universities) in Latin America (Argentina, Bolivia, Colombia, Costa Rica, Honduras, Mexico, Paraguay, Peru, and Uruguay). Eligible women were aged 30-64 years, sexually active, did not have a history of cervical cancer or treatment for cervical precancer or a hysterectomy, and were not planning to move outside of the study area. Women were screened with HPV DNA testing and cytology. HPV-positive women were referred to colposcopy using a standardised protocol, including biopsy collection of observed lesions, endocervical sampling for transformation zone (TZ) type 3, and treatment as needed. Women with initial normal colposcopy or no high-grade cervical lesions on histology (less than cervical intraepithelial neoplasia [CIN] grade 2) were recalled after 18 months for another HPV test to complete disease ascertainment; HPV-positive women were referred for a second colposcopy with biopsy and treatment as needed. Diagnostic accuracy of colposcopy was assessed by considering a positive test result when the colposcopic impression at the initial colposcopy was positive minor, positive major, or suspected cancer, and was considered negative otherwise. The main study outcome was histologically confirmed CIN3+ (defined as grade 3 or worse) detected at the initial visit or 18-month visit. Between Dec 12, 2012, and Dec 3, 2021, 42 502 women were recruited, and 5985 (14·1%) tested positive for HPV. 4499 participants with complete disease ascertainment and follow-up were included in the analysis, with a median age of 40·6 years (IQR 34·7-49·9). CIN3+ was detected in 669 (14·9%) of 4499 women at the initial visit or 18-month visit (3530 [78·5%] negative or CIN1, 300 [6·7%] CIN2, 616 [13·7%] CIN3, and 53 [1·2%] cancers). Sensitivity was 91·2% (95% CI 88·9-93·2) for CIN3+, whereas specificity was 50·1% (48·5-51·8) for less than CIN2 and 47·1% (45·5-48·7) for less than CIN3. Sensitivity for CIN3+ significantly decreased in older women (93·5% [95% CI 91·3-95·3] in those aged 30-49 years vs 77·6% [68·6-85·0] in those aged 50-65 years; p<0·0001), whereas specificity for less than CIN2 significantly increased (45·7% [43·8-47·6] vs 61·8% [58·7-64·8]; p<0·0001). Sensitivity for CIN3+ was also significantly lower in women with negative cytology than in those with abnormal cytology (p<0·0001). Colposcopy is accurate for CIN3+ detection in HPV-positive women. These results reflect ESTAMPA efforts in an 18-month follow-up strategy to maximise disease detection with an internationally validated clinical management protocol and regular training, including quality improvement practices. We showed that colposcopy can be optimised with proper standardisation to be used as triage in HPV-positive women. WHO; Pan American Health Organization; Union for International Cancer Control; National Cancer Institute (NCI); NCI Center for Global Health; National Agency for the Promotion of Research, Technological Development, and Innovation; NCI of Argentina and Colombia; Caja Costarricense de Seguro Social; National Council for Science and Technology of Paraguay; International Agency for Research on Cancer; and all local collaborative institutions.

CIN2 + detection in high-risk HPV patients with no or minor cervical cytologic abnormalities: a clinical approach validated by machine learning

PurposeTo evaluate the feasibility and diagnostic value of the combination of colposcopy, cytology and hrHPV (high-risk human papilloma virus) PCR (polymerase chain reaction) testing in patients with no or minor cytologic abnormalities and HPV high risk infection and to find the best predictors for the presence of CIN2 + in this patient collective.MethodsThree hundred and thirty-four hrHPV patients with normal cytology or minor cytologic abnormalities who had a colposcopic examination at the center of colposcopy at the university hospital Aachen in 2021 were enrolled in this retrospective cohort analysis. Multivariate logistic regression and a machine-learning technique (random forests, leave-one-out analysis) were used.ResultsThe overall risk for CIN2 + in hrHPV-positive patients with normal cytology was 7.7% (N = 18) (5% for CIN3 +), 18% (N = 16) (10.1% for CIN3 +) in patients with PAP IIp (ASC-US) and 62.5% (N = 5) (25% for CIN3 +) in patients with PAP IIg (AGC). Variables that show a statistically significant influence for the CIN-status are ‘major change’ as the result of colposcopy, transformation zone type T1, PAP IIg upon referral (AGC) and hrHPV category 1a (HPV 16/18) detection. Using machine learning (random forests) techniques, the main influencing variables were confirmed. A monotonously decreasing risk for CIN2 + from hrHPV category 1a to 3 (in accordance to the IACR guidelines) was found.ConclusionIn the collective of hrHPV patients with no or minor cytologic abnormalities, the result of colposcopy and HPV PCR status are key predictors for the detection of CIN2 + with a monotonously decreasing risk for CIN2 + from hrHPV category 1a to 3.

Analysis of the cervical microbiome in women from the German national cervical cancer screening program

PurposeCervical cancer (CC) is caused by a persistent high-risk human papillomavirus (hrHPV) infection. The cervico-vaginal microbiome may influence the development of (pre)cancer lesions. Aim of the study was (i) to evaluate the new CC screening program in Germany for the detection of high-grade CC precursor lesions, and (ii) to elucidate the role of the cervico-vaginal microbiome and its potential impact on cervical dysplasia.MethodsThe microbiome of 310 patients referred to colposcopy was determined by amplicon sequencing and correlated with clinicopathological parameters.ResultsMost patients were referred for colposcopy due to a positive hrHPV result in two consecutive years combined with a normal PAP smear. In 2.1% of these cases, a CIN III lesion was detected. There was a significant positive association between the PAP stage and Lactobacillus vaginalis colonization and between the severity of CC precursor lesions and Ureaplasma parvum.ConclusionIn our cohort, the new cervical cancer screening program resulted in a low rate of additional CIN III detected. It is questionable whether these cases were only identified earlier with additional HPV testing before the appearance of cytological abnormalities, or the new screening program will truly increase the detection rate of CIN III in the long run. Colonization with U. parvum was associated with histological dysplastic lesions. Whether targeted therapy of this pathogen or optimization of the microbiome prevents dysplasia remains speculative.

Genotype heterogeneity of high-risk human papillomavirus infection in Ethiopia.

Cervical cancer is a vaccine-preventable sexually transmitted disease. In the year 2020, there were an estimated 604,000 new cases and 342,000 deaths worldwide. Although its incidence is global, it is much higher in sub-Saharan African countries. In Ethiopia, there is a scarcity of data about the prevalence of high-risk HPV infection and its association with cytological profiles. Therefore, this study was conducted to fill this information gap. A hospital-based cross-sectional study was conducted from April 26 to August 28, 2021, and enrolled 901 sexually active women. Socio-demographic and other relevant bio-behavioral and clinical data were collected using a standardized questionnaire. Visual inspection with acetic acid [VIA] was done as an initial screening method for cervical cancer. The cervical swab was then collected using L-Shaped FLOQSwabs in eNAT nucleic acid preservation and transportation medium. A Pap test was done to determine the cytological profile. Nucleic acid was extracted using STARMag 96 ProPrep Kit on SEEPREP32. A Real-time multiplex assay was performed to amplify and detect the HPV L1 gene used for genotyping. The data were entered into Epi data version 3.1 software and exported to STATA version 14 for analysis. A total of 901 (age range from 30 to 60 years, mean age = 34.8 years, and SD± 5.8) women were screened for cervical cancer using VIA and 832 women had a valid co-testing (Pap test and HPV DNA testing) results for further process. The overall prevalence of hr HPV infection was 13.1%. Out of 832 women, 88% of them had normal and 12% had abnormal Pap test results. The proportion of high risk HPV was significantly higher among women with abnormal cytology (X 2 = 688.446, p < 0.001) and younger age (X 2 = 15.3408, p = 0.018). Among 110 women with hr HPV, 14 genotypes (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, and -68) were identified while HPV-16, -31, -52, -58, and -35 genotypes were highly prevalent. The high risk HPV infection continues to be a significant public health problem among women 30-35 years old. The presence of high-risk HPV irrespective of genotypes is highly correlated with cervical cell abnormalities. Genotype heterogeneity is observed suggesting the importance of periodic geospatial genotyping surveillance for vaccine effectiveness.

Natural History of Anal HPV Infection in Women Treated for Cervical Intraepithelial Neoplasia.

Women with high-grade squamous intraepithelial lesions/cervical intraepithelial neoplasia (HSIL/CIN) are at high risk of anal human papillomavirus HPV infection, and it has also been suggested that self-inoculation of the virus from the anal canal to the cervix could explain HPV recurrence in the cervix after treatment of HSIL/CIN. We aimed to evaluate the bidirectional interactions of HPV infection between these two anatomical sites. We evaluated 68 immunocompetent women undergoing excisional treatment for HSIL/CIN. Immediately before treatment, samples from the anus and the cervix were obtained (baseline anal and cervical HPV status). Cervical HPV clearance after treatment was defined as treatment success. The first follow-up control was scheduled 4-6 months after treatment for cervical and anal samples. High resolution anoscopy (HRA) was performed on patients with persistent anal HPV infections or abnormal anal cytology in the first control. Baseline anal HPV was positive in 42/68 (61.8%) of the women. Anal HPV infection persisted after treatment in 29/68 (42.6%) of the women. One-third of these women (10/29; 34.5%) had HSIL/anal intraepithelial neoplasia (AIN). Among women achieving treatment success, cervical HPV in the first control was positive in 34.6% and 17.6% of the patients with positive and negative baseline anal HPV infection, respectively (p = 0.306). In conclusion, patients with persisting anal HPV after HSIL/CIN treatment are at high risk of HSIL/AIN, suggesting that these women would benefit from anal exploration. The study also suggests that women with anal HPV infection treated for HSIL/CIN might be at higher risk of recurrent cervical HPV even after successful treatment.

Maximizing the cost-effectiveness of cervical screening in the context of routine HPV vaccination by optimizing screening strategies with respect to vaccine uptake: a modeling analysis

BackgroundRegarding primary and secondary cervical cancer prevention, the World Health Organization proposed the cervical cancer elimination strategy that requires countries to achieve 90% uptake of human papillomavirus (HPV) vaccines and 70% screening uptake. The optimal cervical screening strategy is likely different for unvaccinated and vaccinated cohorts upon national HPV immunization. However, health authorities typically only provide a one-size-fits-all recommendation for the general population. We aimed to evaluate the cost-effectiveness for determining the optimal screening strategies for vaccinated and unvaccinated cohorts.MethodsWe considered the women population in Hong Kong which has a unique HPV infection and cervical cancer epidemiology compared to other regions in China and Asia. We used mathematical models which comprise a deterministic age-structured compartmental dynamic component and a stochastic individual-based cohort component to evaluate the cost-effectiveness of screening strategies for cervical screening. Following the recommendations in local guidelines in Hong Kong, we considered strategies that involved cytology, HPV testing, or co-testing as primary cervical screening. We also explored the impacts of adopting alternative de-intensified strategies for vaccinated cohorts. The 3-year cytology screening was used as the base comparator while no screening was also considered for vaccinated cohorts. Women’s lifetime life years, quality-adjusted life years, and costs of screening and treatment were estimated from the societal perspective based on the year 2022 and were discounted by 3% annually. Incremental cost-effectiveness ratios (ICERs) were compared to a willingness to pay (WTP) threshold of one gross domestic product per capita (US $47,792). Probabilistic and one-way sensitivity analyses were conducted.ResultsAmong unvaccinated cohorts, the strategy that adds reflex HPV to triage mild cytology abnormality generated more life years saved than cytology-only screening and could be a cost-effective alternative. Among vaccinated cohorts, when vaccine uptake was 85% (based on the uptake in 2022), all guideline-based strategies (including the cytology-only screening) had ICERs above the WTP threshold when compared with no screening if the vaccine-induced protection duration was 20 years or longer. Under the same conditions, HPV testing with genotyping triage had ICERs (compared with no screening) below the WTP threshold if the routine screening interval was lengthened to 10 and 15 years or screening was initiated at ages 30 and 35 years.ConclusionsHPV testing is a cost-effective alternative to cytology for vaccinated cohorts, and the associated optimal screening frequency depends on vaccine uptake. Health authorities should optimize screening recommendations by accounting for population vaccine uptake.

Pattern and predictors of cervical epithelial cell abnormalities among unscreened and under-screened women in Lagos, Nigeria: a cross-sectional study.

Women who had never undergone cervical screening (CS) or who have infrequent CS are at increased risk of having cervical epithelial cell abnormalities (CECA) that may lead to cervical cancer (CCa). Our study determined the pattern and factors that predict the occurrence of CECA among unscreened and under-screened women in Lagos, Nigeria. This was an analytical cross-sectional study among 256 consenting sexually active women between 21 and 65 years who attended a community CS programme in Surulere, Lagos, Nigeria, in June 2019. Information on socio-demographic, reproductive, sexual, behavioural and clinical characteristics were collected and a Pap smear test was done. Women with abnormal cervical cytology were followed up and given appropriate treatment. Data analysis was done using Statistical Package for Social Sciences version 23. Descriptive statistics were computed using frequencies and association was tested using odd ratio. The participants' mean age was 42.7 ± 10.3 years, majority were married (79.9%) and were human immune deficiency syndrome (HIV) negative (63.1%). The prevalence of CECA was 9.8%. Atypical squamous cell of undetermined significance and atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion were the most common CECA with prevalence rates of 7.4% and 2.0%, respectively. Having a partner with multiple sexual partners (adjusted odd ratio (AOR) = 19.23), being HIV positive (AOR = 25.61), giving birth for the first time before the age of 26 years (AOR = 5.55) and presence of a combination of either abnormal vaginal discharge, contact bleeding or an unhealthy cervix on clinical examination (AOR = 13.65) independently predicted the occurrence of CECA. There is a need to prioritise CS for women with these risk factors to prevent CCa and reduce the burden of the disease in our environment.

Underscreening, Overscreening, and Guideline-Adherent Cervical Cancer Screening in a National Cohort

ABSTRACT Cervical cancer screening is highly effective in reducing incidence and mortality of cervical cancer. Recommended cervical cancer screening involves cytology alone every 3 years between the ages of 21 and 29 years and with either human papillomavirus (HPV) testing alone or HPV plus cytology cotesting every 5 years or cytology alone ever 3 years for individuals of average risk between the ages of 30 and 65 years. Overscreening may result in subsequent overtreatment and increased costs, whereas underscreening may lead to lack of repeat testing after abnormal cytology or HPV test and increased incidence of preventable cervical cancer. This retrospective study aimed to identify high-risk individuals who require more frequent screening and to examine rates of underscreening, overscreening, and guideline-adherent screening among women of average risk for cervical cancer. Data were obtained on women aged 21 to 64 years with continuous insurance coverage between 2014 and 2019 from the IBM MarketScan Commercial Claims and Encounters Database (MarketScan). Claims data were examined for low- and high-risk conditions, where low risk was defined as having undergone a hysterectomy, and high risk was defined as the presence of 1 or more conditions requiring more frequent screening including abnormal screening history, HIV-positive status, and solid organ transplant. Among average-risk women, underscreened was defined as Papanicolaou (Pap) tests recorded at &lt;3.5- to 5-year intervals or HPV testing or cotesting at &lt;5.5-year intervals, and overscreened as Pap tests recorded at &lt;2.5-year intervals or HPV testing or cotesting at 2.5- to 4.5-year intervals. Logistic regression was used to determine the association between women's demographic and clinical characteristics and the odds of receiving appropriate screening, underscreening, and overscreening. A total of 1,872,809 women were identified and included in the analysis, of whom 401,746 (22%) did not qualify for routine screening. Of these, 72,684 (4%) had evidence of hysterectomy without a cancer diagnosis, and 329,062 (18%) required more frequent screening due to high-risk medical conditions or prior screening abnormalities. A total of 1,471,063 women (79%) qualified for routine screening; however, 373,368 (25%) of them had no record of screening during the study time frame. Of the 278,938 women (19%) screened with Pap tests alone, 15% received guideline-adherent screening, 44% were underscreened (screened &gt;3.5- to 5-year interval), 41% were overscreened (2.5- to 4.5-year interval), and 3% were severely underscreened (&lt;5-year interval). Of the 493,028 women (33%) screened with HPV/Pap cotesting, 44% were guideline-adherent, 51% were overscreened, 33% were severely overscreened (&lt;2.5-year interval), and 5% were underscreened. Logistic regression revealed women aged 30 to 39 years were more likely to receive guideline-adherent screening than other age groups (odds ratio [OR], 0.72, 0.87, and 0.71, with 95% confidence intervals [CIs] of 0.70–0.73, 0.86–0.88, and 0.70–0.72 for women aged 20–29, 40–49, and 50–64 years, respectively). Women with 1, 2, or 3 comorbidities had higher odds of appropriate screening compared with women with no comorbidities (OR, 1.18 [95% CI, 1.16–1.19], 1.15 [1.13–1.16], and 1.11 [1.09–1.13], respectively). Each additional gynecological visit was associated with lower odds of guideline-adherent screening (OR, 0.78; 95% CI, 0.78–0.78), whereas each preventive care visit was associated with higher odds of guideline adherence (OR, 1.06; 95% CI, 1.05–1.06). The results of this study demonstrated that nearly 1 in 5 women had high-risk conditions necessitating more frequent screening and that only 1 in 5 average-risk women were screened according to guidelines, with high rates of underscreening particularly among women 50 years and older.

The association of Chlamydia trachomatis and human papillomavirus co-infection with abnormal cervical cytology among women in south of Morocco.

Evidence indicates that human papillomavirus (HPV) and Chlamydia trachomatis (CT) co-infection increases the risk of developing cervical pathogenesis. This study aims to assess the prevalence and possible risk factors of CT and HPV/CT co-infection in women from South of Morocco with normal and abnormal cytology. Participants were recruited after signing an informed consent. Cervical samples were collected and analysed for the presence of HPV or CT. Detection of genomic DNA of both pathogens was performed by nested polymerase chain reaction. HPV genotypes defined by Sanger sequencing method. The association between demographic features and co-infection status was determined using a logistic regression model. A possible association between the presence of HPV and CT and cytological abnormality patterns was also investigated. We recruited n=438 women, aged between 18 and 86 years. Around 59% of participants underwent a pap smear test for the first-time. Genomic DNA of HPV, CT and HPV/CT co-infection was detected in 32.3%, 17.7%, and 13.4% of the total samples, respectively. The identified risk factors associated with CT infection were history of sexually transmitted infections and marital status. By contrast, only smoking was found to be associated with HPV/CT co-infection. Evidence showed that co-infection was associated with an increased risk of developing cervical abnormalities (OR 3.18, 95% CI 0.96-9.21; p=0.040). HPV and CT rates were high among the studied population. Evidence suggests that HPV/CT co-infected women were more susceptible to developing abnormal cytology.

Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget's Disease of the Vulva: A Referral Center Experience.

Cervico-vaginal (CV) localization of extra-mammary Paget's disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5-8.0%) at 5 years, 6.5% (95% CI: 1.9-15.1%) at 10 years and 14.0% (95% CI: 4.8-27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget's disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up.

Diagnostic comparison of electrical impedance spectroscopy with colposcopy and HPV mRNA-testing in the prediction of CIN2+ women in Greece.

To compare the diagnostic parameters of electrical impedance spectroscopy (EIS) via ZedScan, a device that measures spectra to differentiate between normal and abnormal cervical tissues, when used as an adjunct to colposcopies in the diagnosis of HSILs/CIN2+ in Greek women with abnormal referral cytology toward colposcopy alone and HPV mRNA-testing. This study analyzed 86 women, patients of the Colposcopy and Cervical Pathology Clinic of 2nd Obstetrics and Gynecology Department, Aristotle University of Thessaloniki at Hippokration General Hospital, between January 2022 and September 2022. During the visits, women were subjected to cytology, colposcopy alone and then with EIS/ZedScan and histological sampling. Common use of colposcopies and EIS/ZedScan allowed detecting an additional 14 cases of CIN2+ (16.2%) that colposcopy alone failed to report. EIS enhanced the sensitivity of colposcopy from 80.65% to 100% equal with that of HPV-mRNA test while retaining a high specificity (94.74%) which is much higher than specificity of HPV mRNA-testing (65.45%). EIS-assisted colposcopy had the highest value combination of positive and negative predictive values (96.15% and 100%) compared to colposcopy alone (100% and 75%) and HPV mRNA-testing (72.46% and 100%). Colposcopies performed with EIS/ZedScan demonstrated effectiveness in the diagnosing of CIN2+ leading to a significant increase in the number of CIN2+ that would have been missed if only colposcopy was applied especially in women with LSIL referral cytology. EIS/ZedScan seems to possess the ideal diagnostic threshold for sensitivity, specificity, and predictive values for CIN2+ compared to colposcopy alone and HPV mRNA-testing.

The vaginal microbiota of women living with HIV on suppressive antiretroviral therapy and its relation to high-risk human papillomavirus infection

BackgroundFew studies have investigated the vaginal microbiota (VM) in women living with HIV (WLWH) in the context of high-risk human papillomavirus (HR-HPV) infection, even though WLWH are at an increased risk of HPV-related malignancies, including cervical cancer. To explore the impact of HIV and HPV infection on the VM in WLWH, we determined the prevalence of HR-HPV infection and cervical cytologic abnormalities in a cohort of 44 WLWH and 39 seronegative-women (SNW), characterized the vaginal microbiota by 16S sequencing, assessed genital inflammation and systemic immune activation by multiplex bead assay and flow cytometry, respectively. Finally, we explored relationships between bacterial richness and diversity, the top 20 bacterial genera, genital inflammation and systemic immune activation.ResultsWe found that HR-HPV prevalence was similar between WLWH and SNW. High-grade squamous intraepithelial lesions (HSIL) were only detected in WLWH negative for HR-HPV infection. In regression analyses, no risk factors were identified. Women co-infected with HIV and HR-HPV had the highest level of systemic immune activation, and these levels were significantly different compared with SNW without HR-HPV infection. Lactobacillus iners was the dominant Lactobacillus species in WLWH and SNW alike.ConclusionWe found no evidence of differences in vaginal microbial richness and diversity, microbial community structure, and genital inflammation by HIV, HPV, or HIV and HPV status.