Cervical Cytology Research Articles

Long-term follow-up of cervical cancer incidence after normal cytological findings.

An increase in cervical cancer incidence in Sweden from 2014 to 2015 has been attributed to an increase in false-negative cytological findings before cancer diagnoses. Years later, we performed a long-term follow-up to investigate whether the problem persisted. At each calendar year from 2016 to 2020, we identified women with prior normal cervical screening results through linkage to the Swedish National Cervical Screening Registry. We reported their incidence rates (IRs) of invasive cervical cancer in consecutive years and compared the IRs over time. For the years 2016 to 2020, there was no overall change in cervical cancer incidence after two normal cytology in the last two screening intervals. However, there was a further 62% increase among women 50 to 60 years of age with normal cytology in the past two screening intervals. The incidence rate of cervical cancer was high among nonscreened women and low among HPV-screened women with negative results, with no trends over time. Our results imply that the previously reported decrease in sensitivity of cervical cytology is persisting. Although primary cytology screening is no longer used, cytology is used in triaging among HPV-positive women. Our findings suggest that improved triaging is needed, for example, improved quality assurance and/or use of alternative triage tests.

Characteristics of Women Seeking Cervical Cancer Cytology Screening in a Private Health Facility.

Background and Objectives: Over 80% of cervical cancer cases in sub-Saharan Africa are detected at late stages, predominantly due to the lack or inaccessibility of prevention services. Public health facilities in Ethiopia offer free cervical cancer screening for eligible women. Besides the public health facilities, private providers also offer a variety of screening services at the patients' expense. As the overall cervical cancer screening uptake in Ethiopia is still far below the 90% WHO target, coordination between all actors of the health system is key. This includes a close cooperation between the public and private sectors to combine the advantages of both to the benefit of all patients as well as media campaigns and community involvement to promote the self-initiation of screening. Materials and Methods: To gain insights into the utilization of cervical cancer screening in the private health sector, we conducted an institution-based cross-sectional study at Arsho medical laboratories in Addis Ababa. Every woman who came there for cervical cancer screening between 1 May and 30 June 2020 was asked to participate in a questionnaire-based, face-to-face interview about their socio-demographic background, cervical cancer screening experience and self-initiation of screening. A total of 274 women participated in the interviews. We further assessed the reproductive status of the patients, their risk factors for cervical cancer, source of information about the screening and barriers to cervical cancer screening. Results: The ages of the participants ranged between 20-49 years. The majority (over 70%) were married. A total of 37.6% reported self-initiating the screening. More than three-quarters of all interviewed women reported mostly using the private health care sector for all kinds of health services. Conclusions: While the Ethiopian government efforts on scaling up cervical cancer screening focus mainly on public health facilities, the private sector often does not get as much attention from policy makers. Efforts should be made to extend the government's interest in cervical cancer screening and implementation research to the private healthcare sector.

Exploring the prevalence of Human Papillomavirus (HPV) genotypes in PAP smear samples of women in northern region of United Arab Emirates (UAE): HPV Direct Flow CHIP system-based pilot study.

The aim of this study was to explore the prevalence of low and high-risk HPV genotypes in PAP smear samples of women in northern region of the UAE using HPV direct flow CHIP method. A cross-sectional retrospective study was conducted between September 2021 to April 2022. A total of 104 liquid-based cervical cytology samples were obtained from women aged 20-59 years attending the Gynaecology out-patient department of Thumbay University Hospital and other hospitals of Northern Emirates of UAE, processed for the routine cytological examination to identify and differentiate morphological changes of the PAP smear samples. HPV genotyping was performed using HPV direct flow CHIP method. In total, 112 HPV genotypes were detected in 63 women (60.57%) included 18 abnormal cytological and 45 normal epithelial samples. 63 LR and 49 HR HPV genotypes were identified in all the 63 positive samples. Highest rate of infection with multiple LR and HR HPV genotypes were detected in women aged 40-49 years (25.9%) and 20-29 years (23.5%). Infection by HPV6 (13.46%), HPV11 (9.61%), HPV16 (9.61%), HPV62/81 (7.69%) and HPV45 (7.69%) were the most common genotypes. A moderate increase than expected incidence of HPV45 and 62/81 (7.69%) were detected. Co-infection with multiple low and high-risk genotypes is present in 20.2% cases; in that, HPV6 (15.9%) was the most common followed by HPV62/81 (12.7%) and HPV16 (11.11%). The prevalence of HPV18 was found to be 1.6%. The genotypes 6, 45, 16, 11, 67, 62/81 were the most common HPV infections in the women between the age group of 21 and 59-years-old. A moderate increase of HPV45, 62/81 and much less prevalence of HPV18 were detected in the study population. 43.27% of the normal epithelia were positive to different low and high-risk HPV genotypes. This finding highlights the importance of molecular genotyping of HPV to emphasize the cervical screening triage.

Use of grape-based stain (Vinatela) on cervical cytology: A Peruvian validation study.

The Papanicolaou's (Pap's) stain is used for cervical cancer screening. It employs toxic-carcinogenic expensive reagents, which may not be easily accessible to many communities worldwide. The objective of this study was to validate the grape-based alcohol-extracted dye (Vinatela) on normal cervical samples for the Pap test. Samples of the two grape species were collected from two vineyards through the Agroindustrial Research Institute of Universidad Privada San Juan Bautista. The dye extraction from the grape species and the dye performance to stain cells were conducted in three phases: (a) direct staining with pre-fermentation wine products, (b) direct fragmentation of grapes and direct staining with shells of the grapes, and (c) alcoholic extraction of the dye. Vinatela obtained from two species (Vitis vinifera "Tempranillo" and "Malbec") and posterior staining of cervical samples. We conducted a double-blind validation on 30 cervical samples. The basophilic components of the cervical cells were stained. Alcoholic extraction staining protocol had a low yield. The nuclear and cytoplasmic borders, the nuclear details, and the polymorphonuclear nuclei were stained with Vinatela and could be differentiated during nuclear coloration. The initial staining protocol was 10- 20 min × (mean ~12 min) staining time. We noted a slightly better staining with V. v. Tempranillo as compared to V. v. Malbec (P = 0.045). Cervical cells stained with Vinatela stain from two grape species cultivated in the Southern of Peru, showed basophilic nuclear details.

Are HPV-negative lesions concerned for the introduction of primary HPV testing for cervical cancer screening in Japan?

In Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV-negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high-risk HPV- (CIN2+/hrHPV-) cases in cervical cancer screening. Data from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low-grade squamous intraepithelial lesion (LSIL+)/hrHPV- were analyzed in detail. The results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV-, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC-US)/hrHPV-, 213 were ASC-US/hrHPV+, 291 were LSIL+/hrHPV-, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV- examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV- was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric-type adenocarcinoma was not included. HPV-negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national-level management system need to be established.

Usefulness of the human papillomavirus DNA chip test as a complementary method for cervical cytology.

As a convenient and economical method of screening cervical cancer and precancerous pathologies, the Papanicolaou smear (Pap smear) has been most widely used. Nevertheless, it requires cytological changes for making diagnoses and reportedly has a high false-negative rate. In this study, the usefulness of the human papillomavirus (HPV) DNA chip test as a complementary method that can compensate for the defect of the Pap smear was investigated. Of the 6516 patients who simultaneously underwent a Pap smear and an HPV DNA chip test at Chonnam National University Hospital between January 2015 and December 2016, 1897, an initial PAP smear-negative patients who had undergone an additional Pap smear during their 2-year follow-up period were selected for this study. Of the subject patients, 281 underwent a cervical biopsy. The Pap smear follow-up of an initial Pap smear-negative subjects showed 53 (75.7%) HPV high-risk positive cases in the cytology low-grade lesion group (70 cases) and 46 (97.8%) HPV high-risk positive cases in the cytology high-grade lesion group (47 cases). The 281 biopsy cases included 67 biopsy low-grade lesion cases and 74 biopsy high-grade lesion cases, of which there were 45 (67.2%) and 67 (90.5%) HPV high-risk positive cases, respectively. The follow-up cytology on the high-risk HPV-positive subjects showed that the ratio of their high-grade lesions was 260.8 times greater than that of the high-risk HPV-negative subjects (OR = 260.8 and 95% CI: 36.1 and 1886.1); and their biopsy showed that the ratio of their high-grade lesions was 102.7 times greater than that of the HPV-negative subjects (OR = 102.7 and 95% CI: 14.0 and 753.3). The complementary use of the HPV DNA chip test may be useful in increasing the accuracy of screening examinations for the early diagnosis of uterine cervix cancer when combined with the Pap smear.

Atypical Endometrial Cells in Cervical Cytology: Correlation with Surgical Follow-up

Atypical Endometrial Cells in Cervical Cytology: Correlation with Surgical Follow-up

Assessment of Human Papillomavirus Non-16/18, Type-Specific Risk for Cervical Intraepithelial Neoplasia Grade 3 or Worse Among Women With Cervical Atypical Glandular Cells.

To evaluate the risk for cervical intraepithelial neoplasia grade 3 (CIN 3) or worse (including adenocarcinoma in situ [AIS] and invasive cervical cancer) associated with non-16/18 human papillomavirus (HPV) types (other HPV) among women with atypical glandular cells (AGC) in cervical cytology. This population-based cohort study evaluates the risk of CIN 3 or worse associated with other HPV types. Human papillomavirus genotyping was performed on Pap tests collected in Sweden from 341 women with AGC that were positive for other HPV types from February 17, 2014, to December 31, 2018. The women were followed for histopathologic outcomes using comprehensive registry linkages until December 31, 2019. Cumulative incidence proportions of CIN 3 or worse by specific HPV type were calculated using 1-minus Kaplan-Meier function. Hazard ratios (HRs) for CIN 3 or worse were generated using multivariate Cox regression. Of 341 women, 134 (39.3%) had CIN 3-AIS, but there were only five (1.5%) women in the cohort with invasive cervical cancer. Human papillomavirus 45 preceded 80.0% of invasive cervical cancer cases. Among women positive for HPV33, 82.9% (95% CI 58.0-97.3%) had CIN 3 or worse during follow-up. Positivity for HPV31 conferred the highest HR for CIN 3 or worse relative to other types, both in primary cytology and primary HPV screening (HR 2.71, 95% CI 1.47-5.00 and HR 3.41, 95% CI 1.95-5.96, respectively). Among non-16/18 HPV types in AGC, HPV31 and 33 had the highest risk for CIN 3 or worse, whereas most of the women with invasive cancer were positive for HPV45. Extended HPV genotyping may be helpful for the management of AGC.

Overtreatment in the see-and-treat approach for high-grade squamous cervical cytology.

To evaluate overtreatment with the 'see-and-treat' approach in patients with high-grade squamous cervical cytology, and identify the clinical factors associated with overtreatment. Patients with high-grade squamous intra-epithelial lesion (HSIL) cytology undergoing colposcopy and loop electrosurgical excision procedure (LEEP) in a single visit or the 'see-and-treat' approach from January 2005 to December 2019 were reviewed retrospectively. The overtreatment rate and complications following LEEP were explored. In total, 220 cases were identified. The overtreatment rate was 11.4%, and surgical complications were haemorrhage (n=3, 1.36%) and infection (n=9, 4.09%). On univariable analysis, factors associated with overtreatment were current cytological result and colposcopic impression. On multi-variable analysis, current cytological result of non-HSIL compared with HSIL/cancer, and colposcopic diagnosis of low-grade lesion or normal compared with high-grade lesion or cancer had adjusted odds ratios of 13.81 [95% confidence interval (CI) 1.23-155.20; p=0.033] and 3.58 (95% CI 1.32-9.74; p=0.013), respectively. The overtreatment rate with the 'see-and-treat' approach was 11.4%. Independent factors associated with overtreatment were current cervical cytological result of non-HSIL, and low-grade or normal colposcopic diagnosis.

Role of Ureaplasma urealyticum and Ureaplasma parvum as Risk Factors for Cervical Dysplasia with Human Papillomavirus

Human papillomavirus (HPV) can be transmitted sexually and causes cervical malignancies in women. Among the risk factors, sexually transmitted infections (STIs) caused by bacteria have raised concerns because they are asymptomatic and persistent and can increase the risk of HPV infection. This study assessed the correlation among Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, and Mycoplasma hominis infections towards abnormal cervical cells positive for HPV. Seventy outpatients at the Colposcopy Outpatient Clinic, Dr. Cipto Mangunkusumo Hospital in Jakarta, Indonesia, were enrolled in this cross-sectional study. Viruses and bacteria were detected using polymerase chain reaction and compared with liquid-based cytology results for cervical cytology. Of the 70 patients, 24 (34.28%) showed abnormal cervical cytology. Among those with abnormal cervical cytology, C.trachomatis was reported in 1 patient (4.2%), M.hominis in 6 patients (25%), U.urealyticum in 13 patients (54.2%), and U.parvum in 10 patients (41.7%). Statistical analysis demonstrated an association between U.urealyticum and U.parvum infections and HPV infection (U.urealyticum p = 0.012; U.parvum p = 0.022). U.urealyticum and U.parvum were more prevalent than C.trachomatis and M.hominis in HPV-positive women, suggesting their role in HPV infection.

A Study of Cervical Cytology on Pap Smears with Positive High-risk Human Papillomavirus (hrHPV) Tests with Non-HPV 16/18/45 Subtypes

A Study of Cervical Cytology on Pap Smears with Positive High-risk Human Papillomavirus (hrHPV) Tests with Non-HPV 16/18/45 Subtypes

Prevalence of high-risk human papillomavirus infections and cervical pathology in women with ASC-US cervical cytology

Background and aims: This study identified the prevalence of high-risk human papillomaviruses (hrHPV) and pathological diagnosis variation among patients with ASC-US. Materials and Methods: This Cross-sectional descriptive study recruited 569 female participants aged 21-68 years who attended Tu Du Hospital from 10/2019 to 12/2020 and performed PAP smear tests diagnosed as ASC-US. Results: The prevalent rate of hrHPV infection was 44.8%. Regardless of HPV 16 and HPV 18, the infection rate of the remaining hrHPV was predominant (71.4%, 182/255), followed by the 10.6% of HPV 16 and the 4.3% HPV 18. Among 175 patients having cervical pathology, the rate of squamous cell carcinoma, cervical intraepithelial neoplasia CIN 1, CIN 2, and CIN 3 was 1.15%, 4.0%, 5.7%, and 1.15%, respectively. HPV 16 was present in all patients (2/2, 100%) who developed squamous cell carcinoma, and in six of twelve patients (50%) who acquired CIN 2 and 3. The subjects who had been exposed to more than one hrHPV genotype (HPV 16, HPV 18, and others) were diagnosed CIN 2 (40.0%). Despite the high likelihood of infection with other HPVs other than HPV 16 and 18 (75.9%), the majority of participants had normal cervical histology. Conclusion: Patients carrying hrHPV with ASC-US seem to appear diverse histopathological findings in which the incidence of CIN2+ accounts for a large proportion (8%). Key words: ASC-US, high-risk HPV, CIN, cervical cancer.

Improving Mobile-Based Cervical Cytology Screening: A Deep Learning Nucleus-Based Approach for Lesion Detection

Liquid-based cytology (LBC) plays a crucial role in the effective early detection of cervical cancer, contributing to substantially decreasing mortality rates. However, the visual examination of microscopic slides is a challenging, time-consuming, and ambiguous task. Shortages of specialized staff and equipment are increasing the interest in developing artificial intelligence (AI)-powered portable solutions to support screening programs. This paper presents a novel approach based on a RetinaNet model with a ResNet50 backbone to detect the nuclei of cervical lesions on mobile-acquired microscopic images of cytology samples, stratifying the lesions according to The Bethesda System (TBS) guidelines. This work was supported by a new dataset of images from LBC samples digitalized with a portable smartphone-based microscope, encompassing nucleus annotations of 31,698 normal squamous cells and 1395 lesions. Several experiments were conducted to optimize the model’s detection performance, namely hyperparameter tuning, transfer learning, detected class adjustments, and per-class score threshold optimization. The proposed nucleus-based methodology improved the best baseline reported in the literature for detecting cervical lesions on microscopic images exclusively acquired with mobile devices coupled to the µSmartScope prototype, with per-class average precision, recall, and F1 scores up to 17.6%, 22.9%, and 16.0%, respectively. Performance improvements were obtained by transferring knowledge from networks pre-trained on a smaller dataset closer to the target application domain, as well as including normal squamous nuclei as a class detected by the model. Per-class tuning of the score threshold also allowed us to obtain a model more suitable to support screening procedures, achieving F1 score improvements in most TBS classes. While further improvements are still required to use the proposed approach in a clinical context, this work reinforces the potential of using AI-powered mobile-based solutions to support cervical cancer screening. Such solutions can significantly impact screening programs worldwide, particularly in areas with limited access and restricted healthcare resources.

Prevalence of human papillomavirus infection in abnormal pap smears.

This study was undertaken to study the prevalence of human papillomavirus (HPV) infection using the polymerase chain reaction (PCR) technique in abnormal cervical pap smears and to correlate the different cytological results with HPV infection. A total of 1788 cervical pap smears of women more than 30 years of age conducted over a period of 1 year 3 months (June 2015-August 2016) were screened by liquid-based cytology. High-risk (HR)-HPV testing was performed by PCR in abnormal lesions. Inflammatory smears and some atypical squamous cells of undetermined significance (ASCUS)-reactive cases were excluded from HPV testing. Histopathological correlation was done wherever possible. The overall prevalence of the intraepithelial lesions/malignancy was ASCUS. (ASCUS) - 79 (4.42%), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) - 10 (0.56%), low-grade squamous intraepithelial lesion (LSIL) - 26 (1.45%), high-grade squamous intraepithelial lesion (HSIL) - 15 (0.84%), squamous cell carcinoma - 5 (0.28%), and adenocarcinoma - 1 case (0.06%). Overall, 136 (7.60%) samples were classified as abnormal. Seventy-seven samples were included for HR-HPV testing - 20 ASCUS, 10 ASC-H, 26 LSIL, 15 HSIL, and 6 malignant cases. A control group of ten samples with normal cervical cytology within the normal limit (Control) (WNLc) was tested for HR-HPV. HR-HPV was detected in 20% of samples of the WNLc group, 45% of the ASCUS group, 70% of the ASC-H group, 73.07% of the LSIL group, 86.67% of the HSIL, and 83.34% of the samples in the malignant group. Overall, HR-HPV was detected in 68.83% of abnormal cervical pap smears. Our study shows that the percentage of HR-HPV-positive case increases with the severity of cytologic morphology. HPV had 4 times higher positivity in squamous intraepithelial lesion as compared to ASCUS.

Endometrial cancer diagnoses prompted by routine cervical cytology: a retrospective case study.

Endometrial cancer is the commonest gynaecological cancer in New Zealand. Some women have their diagnosis of endometrial cancer prompted by an abnormal cervical cytology screening test. When high-risk human papillomavirus (hr-HPV) testing becomes the primary test for cervical screening, this avenue of incidental diagnosis will be reduced. Therefore, our aims were to estimate the proportion of women whose diagnosis of endometrial cancer follows incidental detection on routine cervical cytology, and to understand the clinicopathologic characteristics of these cases. Retrospective analysis of patient medical records from women of cervical screening age diagnosed with endometrial cancer between 2015-2019 in the South Island of New Zealand. Of 334 women, 26 (7.8%) had endometrial cancer diagnosis prompted by abnormal cervical cytology. Most women had low-grade (17/26, 65.4%), low-stage (18/26, 69.2%) disease of endometrioid histologic subtype (21/26, 80.8%). The small cohort prevented significant correlations with clinicopathologic characteristics and outcomes. Overall, cervical cytology had low sensitivity (32.3%) for the detection of endometrial cancer in the 6 months before diagnosis. A small number of women currently have diagnoses of endometrial cancer prompted by routine cervical screening with cytology. However, the undefined clinical benefit from and poor sensitivity of cervical cytology for detecting endometrial cancer does not justify its use in screening, or opposition to hr-HPV cervical screening.

Cytological DNA methylation for cervical cancer screening: a validation set.

In a previous training set with a case-controlled design, cutoff values for host EPB41L3 and JAM3 gene methylation were obtained for the detection of cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+). This validation trial was conducted to evaluate the role of DNA methylation in screening for CIN2+ by cervical cytology among unselected participants. From June 1, 2019, to September 1, 2019, in our study center, we collected liquid-based samples from cervical swabs for methylation assays and hrHPV testing in eligible patients. The primary endpoint was the diagnostic accuracy of DNA methylation and hrHPV genotyping for CIN2+ according to confirmed histology results. Among 307 participants, compared with hrHPV testing, the methylation assay for CIN2+ had lower sensitivity (68.7% versus 86.1%, p=0.002) but higher specificity (96.7% versus 0.696, p<0.001). The methylation assay also had favorable sensitivity and specificity in patients with negative hrHPV testing (56.3% and 96.9%) and in patients with cervical adenocarcinoma (73.7% and 92.7%). DNA methylation had higher specificity than the hrHPV assay (100.0% versus 44.4%, p<0.001) for identifying residual CIN2+ in patients without residual lesions. Positive cervical DNA methylation was associated with a diagnostic probability of endometrial carcinoma (odds ratio 15.5 [95% confidence interval 4.1-58.6]) but not of ovarian epithelial carcinoma (1.4 [0.3-6.5]). The host EPB41L3 and JAM3 gene methylation assay in cervical cytology had favorable diagnostic accuracy for CIN2+ and was highly specific for residual CIN2+ lesions The methylation assay is a promising triage tool in hrHPV+ women, or even an independent tool for cervical cancer screening. The methylation status in cervical cytology could also serve as a prognostic biomarker. Its role in detecting endometrial carcinomas is worthy of further exploration.

Type distribution of human papillomaviruses in ThinPrep cytology samples and HPV16/18 E6 gene variations in FFPE cervical cancer specimens in Fars province, Iran

BackgroundThere exists strong evidence that human papillomavirus (HPV) is associated with cervical cancer (CC). HPV E6 is a major oncogene whose sequence variations may be associated with the development of CC. There is not sufficient data on the distribution of HPV types in ThinPrep cytology specimens and HPV 16/18 E6 gene variations among CC patients in the southwest of Iran. This study was conducted to contribute to HPV screening and vaccination in Iran.MethodsA total of 648 women screened for cervicitis, intraepithelial neoplasia or CC were included in the study. All participants underwent ThinPrep cytology testing, single-step HPV DNA detection and allele-specific reverse hybridization assays. Moreover, a total of 96 specimens previously tested positive for single infection with HPV16 or 18 were included for variant analysis. HPV16/18 lineages and sublineages were determined by PCR assays followed by sequencing the E6 gene and the construction of neighbor-joining phylogenetic trees.ResultsOverall, HPV DNA was detected in 62.19% of all the screened subjects. The detection rates of HPV DNA among individuals with normal, ASC-US, ASC-H, LSIL, and HSIL cervical cytology were 48.9%, 93.6%, 100%, 100%, and 100%, respectively. Low-risk HPVs were detected more frequently (46.9%) than high-risk (38.9%) and possible high-risk types (11.1%). Of 403 HPV-positive subjects, 172 (42.7%) had single HPV infections while the remaining 231 (57.3%) were infected with multiple types of HPV. Our results indicated a remarkable growth of high-risk HPV66 and 68 and low-risk HPV81 which have rarely been reported in Iran and HPV90 and 87 that are reported for the first time in the country. In addition, 3 lineages (A, D, and C) and 6 sublineages (A1, A2, A4, C1, D1, and D2) of HPV16, and one lineage and 4 sublineages (A1, A3, A4, and A5) of HPV18 were identified. The studied HPV16 and 18 variants mainly belonged to the D1 and A4 sublineages, respectively.ConclusionThe present study suggests that the prevalence of HPV infection in women of all age groups with or without premalignant lesions in the southwestern Iran is high and the predominant HPV types in the southwest of Iran may differ from those detected in other parts of the country. This study also highlights the necessity of not only initiating HPV vaccination for the general population but also developing new vaccines that confer immunity against the prevalent HPV types in the area and national cervical screening programs using a combination of thinPrep cytology test and HPV detection assays in order to improve the accuracy of the screening.

The cervical microbiota of Hispanics living in Puerto Rico is nonoptimal regardless of HPV status.

The cervicovaginal microbiota is influenced by host physiology, immunology, lifestyle, and ethnicity. We hypothesized that there would be differences in the cervicovaginal microbiota among pregnant, nonpregnant, and menopausal women living in Puerto Rico (PR) with and without human papillomavirus (HPV) infection and cervical cancer. We specifically wanted to determine if the microbiota is associated with variations in cervical cytology. A total of 294 women, including reproductive-age nonpregnant (N = 196), pregnant (N = 37), and menopausal (N = 61) women, were enrolled. The cervicovaginal bacteria were characterized by 16S rRNA amplicon sequencing, the HPV was genotyped with SPF10-LiPA, and cervical cytology was quantified. High-risk HPV (HR-HPV, 67.3%) was prevalent, including genotypes not covered by the 9vt HPV vaccine. Cervical lesions (34%) were also common. The cervical microbiota was dominated by Lactobacillus iners. Pregnant women in the second and third trimesters exhibited a decrease in diversity and abundance of microbes associated with bacterial vaginosis. Women in menopause had greater alpha diversity, a greater proportion of facultative and strictly anaerobic bacteria, and higher cervicovaginal pH than premenopausal women. Cervical lesions were associated with greater alpha diversity. However, no significant associations between the microbiota and HPV infection (HR or LR-HPV types) were found. The cervicovaginal microbiota of women living in Puerto Rican were either dominated by L. iners or diverse microbial communities regardless of a woman's physiological stage. We postulate that the microbiota and the high prevalence of HR-HPV increase the risk of cervical lesions among women living in PR. IMPORTANCE In the enclosed manuscript, we provide the first in-depth characterization of the cervicovaginal microbiota of Hispanic women living in Puerto Rico (PR), using a 16S rRNA approach, and include women of different physiological stages. Surprisingly we found that high-risk HPV was ubiquitous with a prevalence of 67.3%, including types not covered by the 9vt HPV vaccine. We also found highly diverse microbial communities across women groups-with a reduction in pregnant women, but dominated by nonoptimal Lactobacillus iners. Additionally, we found vaginosis-associated bacteria as Dialister spp., Gardnerella spp., Clostridium, or Prevotella among most women. We believe this is a relevant and timely article expanding knowledge on the cervicovaginal microbiome of PR women, where we postulate that these highly diverse communities are conducive to cervical disease.

HPV Testing and its Role in Cervical Cancer Screening.

The recognition that persistent infection with carcinogenic human papillomavirus (HPV) is a necessary cause of cervical precancer and cancer has led to the introduction of HPV testing into cervical cancer screening, either as a primary screening test or in conjunction with cervical cytology (i.e., co-testing). HPV testing has much higher sensitivity for detection of cervical precancer and provides greater long-term reassurance if negative compared to cytology. However, most HPV infections are transient, and do not progress to invasive cancer, thus triage tests are required to identify individuals who should be referred to colposcopy for diagnostic evaluation. This chapter begins with a description of the biology, natural history, and epidemiology of HPV as a foundation for understanding the role of HPV in cervical carcinogenesis. This section is followed by a detailed discussion regarding the introduction of HPV-based testing and triage into cervical cancer screening and management. Summarized triage tests include cervical cytology, HPV genotyping, p16/Ki-67 dual stain, and HPV and cellular methylation markers. The final section of this chapter includes an important discussion on cervical cancer disparities, particularly within the United States, followed by concluding remarks.

Long-term clinical significance of benign endometrial cells identified on routine cervical cytology in women aged more or equal to 45 years

Within the Bethesda System, the recommendation of describing benign-appearing endometrial cells (BECs) has changed over recent years. Since the 2014 revision, their presence in cervical cytology reports has been deemed essential, beginning with age 45. Recent studies have suggested rising the reporting age to 50 years. Does the presence of these cells necessitate further assessment? This retrospective cohort study included patients aged between 45 and 65 years in whom BECs were present on cervical cytology between January 2001 and December 2010, with a follow-up at 5 and 10 years. Women who had abnormal cervical cells or atypical endometrial cells on cervical cytology were excluded, as well as women with a history of cervical or endometrial cancer, or a history of hysterectomy and incomplete follow-up data. One hundred seventy-six women were included. Of these, 31% were postmenopausal of which 65% used hormonal substitution therapy. Twenty-eight percent presented with abnormal uterine bleeding at inclusion. During the follow-up period of 10 years, 87.5% had a normal gynecological follow-up and 11.4% underwent a hysterectomy for benign pathology. One percent (2 patients) had been diagnosed with endometrial malignancy, both presenting with postmenopausal bleeding and aged over 60 years. Our study confirmed that the presence of BECs is not a reason for concern when no additional clinical indicator is recognized, especially with normal ultrasonographic examination. Further invasive exploration may be controversial. If reporting BECs in cervical cytology continues, we strongly agree on rising the reporting age to 50 years or postmenopausal state.