Introduction

Lower Anogenital Squamous Terminology (LAST) standardization recommended p16^INK4a immunohistochemistry (p16) on biopsies diagnosed as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSIL). The aim of this investigation was to assess whether p16-positive CIN2 biopsies were similar enough to CIN3 such that making a distinction between the two would be unnecessary.

Methods

The New Mexico HPV Pap Registry selected a state-wide, stratified sample of 4,100 cervical biopsies diagnosed by local community pathologists (CP), including 1,512 CIN2. Biopsies underwent a consensus, expert panel (EP) review (without p16), p16 interpreted by a third pathology group, and HPV genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytology diagnoses were also available. Trends in p16 positivity by biopsy diagnosis or HPV risk groups were calculated.

Results

Biopsies more often tested p16 positive with increasing severity of CP diagnoses, overall (P_trend<.001) and within each HPV risk group (P_trend≤.001). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 positive with a higher HPV risk group (P_trend<.001), and testing p16 positive was associated with higher HPV risk group than testing p16 negative for each grade of CP-diagnosed biopsies (P<.001). p16-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL+ cytology, or to be diagnosed as CIN3+ by the EP (P<.001 for all). p16-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16-negative, CP-diagnosed CIN2 biopsies (P<.001).

Conclusions

p16-positive, CP-diagnosed CIN2 have lower cancer risk than CP-diagnosed CIN3. LAST classification of “HSIL” diagnosis, which includes p16-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions. This is especially true for young women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.

Introduction

p16 immunohistochemistry is recommended for distinction between high-grade and low-grade cervical lesions under the Lower Anogenital Squamous Terminology (LAST), by which CIN2/p16-positive, CIN3, and adenocarcinoma in-situ diagnoses represent histological high-grade intraepithelial lesions (HSIL). Using a LAST-based standardised protocol, we evaluated the inter-observer reproducibility between local and reviewed histological diagnoses within the ESTAMPA study.

Methods

ESTAMPA is a multicentric study in Latin America. Women aged 30-64 are screened with HPV and cytology and referred to colposcopy (with biopsy collection as appropriate) if any screening positive result. Histological slides (H&E) are prepared locally and treatment is offered according to local histologic interpretation. Two expert pathologists blind to local results and additional women’s data reviewed H&E slides following a three-step protocol. If first review disagreed with local interpretation, then a second blind review (along with all slides belonging to the same subject) was done. If first and second reviews disagreed, then a third review between the two experts was done using a multi-head microscope (adjudication meeting). p16 was required at any step as needed. Based on fully reviewed diagnosis, decisions for upgrading (local-based <CIN2 to reviewed-based HSIL+) or downgrading (local-based CIN2+ to reviewed-based <HSIL) were made. Agreement, positive agreement (positive concordant results over total positive results) and unweighted kappa were calculated.

Results

4389 H&E and 196 p16 slides (corresponding to 1716 subjects in 10 study centres) were fully reviewed. The agreement, positive agreement and kappa were 94.5% (95%CI 94.2-95.6), 58.0% (53.8-62.2) and 0.71 (0.67-0.75), respectively. The concordance varied widely among study centres (positive agreement and kappa ranges: 38.3-100, 0.53-1.00). This process led to 26 (2% among 1515) upgrades and 56 (28% among 201) downgrades.

Conclusions

A LAST-based standardised protocol may yield reliable final study endpoints and clinical outcomes. If routinely implemented, it could improve the identification of women in need of urgent treatment reducing overtreatment-related harms.

Introduction

On behalf of the NTCC2 Working Group

The New Technologies for Cervical Cancer 2 (NTCC2) trial aimed at evaluating E6/E7 mRNA overexpression and p16/ki67 dual staining for their performance in triaging HPV-DNA-positive women within organized cervical cancer screening.

Methods

Women were recruited in four centres and tested with HPV-DNA Cobas 4800 or Hybrid Capture 2 assays. HPV-DNA-positive women were triaged with cytology and tested for E6/E7 mRNA and p16/ki67; abnormal cytology referred to colposcopy; negative cytology randomised to immediate colposcopy or 1-year HPV re-testing.

We present immediate colposcopy referral and CIN2+ sensitivity (lesions found within 24 months), with 95% Confidence Interval (95%CI), of cytology [ASCUS+ and high grade (HG) thresholds], E6/E7 mRNA, p16/ki67, and HPV 16-18 typing for women tested with Cobas 4800, alone or in combination. Combinations positivity criteria: “AND” = positivity of both tests, “OR” = positivity for one of the two.

Results

3147/40509 (7.8%) women were HPV-DNA positive (1446 tested with Cobas). Cumulatively, 174 CIN2+ were found (52 among women tested with Cobas).

Table 1. Performance of single and combinations of tests for triage of HPV-DNA positive women

Conclusions

The combination of HPV 16/18 typing with cytology or p16/ki67 resulted in high sensitivity, but with a substantial increase in colposcopy referral compared to single test strategies.

Introduction

The risk of development high-grade lesions and invasive cervical cancer increases with age. Unsatisfactory colposcopy, where the area of interest is not visible in women with a positive cervical screening test , is a common area of clinical uncertainly due to the lack of clear evidence and guidance. In cases of apparent long-term discordance between cytology and unsatisfactory colposcopy (transformation zone type III) a biopsy adequate to make the diagnosis is essential. Endocervical curettage can not be implemented due to cervix stenosis. ECC is further unreliable as a diagnostic procedure when used for the initial assessment of women with ASCUS suggested on cytology. In cause of unclear findings and append request the patients the cone excision were indicated.

Methods

We analyzed retrospectively 776 patients after the cone procedure in group of women between 22 and 80 years old in our clinic.

Results

The main cause for undertaking this medical procedure was pathologically pap smear Pap III D2 (66%) and HPV persistence over 5 Years ( 15,01%). Colposcopy was due to type III transformation zone in over of 99 % unsatisfactory. In our group after the conisation procedure showed in 21 % of cases ( N=26) any pathologically abnormalities, in 6 % of the woman were detected CIN 2+ lesions. We didn’t detect any carcinoma whatsever. Simoultanously 4 cases of VaIN II-III were identify

Conclusions

There is insufficient evidence to support the use of cone biopsy in the triage of high grade intraepithelial lesions in the patients with discrepancy between cytology findings and unsatisfactory colposcopy. However adequate triage methods are releaded to identify those women. The consequent indication for the diagnostic cone procedure must be taken in order to prevent the over-treatment. Anxiety of missing a cancer deters long-term cytological follow-up and resulting in higher than anticipated excisions rate in women with unsatisfactory colposcopy.

Introduction

We compared clinical performance of p16/Ki-67 dual-stained cytology and HPV genotyping, via different algorithms, alone, or in combination with cytology, to identify CIN2+ in women referred to colposcopy at three university-affiliated hospital clinics.

Methods

The STAIN-IT study included 492 (134 normal, 130 CIN1, 99 CIN2, 115 CIN3, 6 CIN2/CIN3, 8 cancers) randomly selected specimens out of 1158 with valid conventional cytology, HPV and biopsy results. Cervical specimens were transferred to PreservCyt solution and tested for presence of high-risk HPV, hrHPV (cobas® 4800 HPV Test). Dual staining (CINtec® PLUS assay) was retrospectively performed; each slide was read by a cytologist and confirmed by two pathologists. Slide readers were blinded to cytology, biopsy, and genotyping results. Accuracy (correct classification rate), sensitivity and specificity (restricted to lesion-free women) and 95% confidence intervals (in parentheses below) of dual-staining to detect CIN2+ were compared with other screening tests available for the same women (HPV, cytology, and combinations), overall and by age (≤30/>30 years).

Results

hrHPV and HPV16/18 positivity were detected in 321 (65.2%) and 139 (28.3%) women, respectively. The overall positivity rate for dual staining was 56.7%; increasing with histological severity from 30.6% in normal, 41.5% in CIN1, 72.7% in CIN2, 87.8% in CIN3 to 87.5% in cancer cases. Dual-stained cytology and hrHPV positivity had similar accuracy [71.8% (67.6-75.7)] in predicting CIN2+; superior to cytology [ASC-US: 65.0 (60.6-69.3); LSIL: 66.7 (62.3-70.8)]. Dual staining alone had lower sensitivity [80.7% (75.0-85.6) vs. 89.9% (85.3-93.5)] and higher specificity [69.4% (60.9-77.1) vs. 64.9% (56.2-73.0)] for CIN2+ compared with hrHPV testing. Combining dual-stained cytology with an ASC-US abnormality threshold, sensitivity increased to 96.1% (92.6-98.2) whereas specificity decreased to 40.3% (31.9-49.1). Corresponding values considering an LSIL threshold were 91.7% (87.3-94.9) and 53.0% (44.2-61.7). Comparable performance patterns were observed between age groups.

Conclusions

Dual-stained cytology and HPV testing had relatively similar performance in predicting CIN2+.

Introduction

FIGO stage IA1 microinvasive cervical cancer (MIC) was traditionally treated with a hysterectomy.

The aim of this study is to compare the results of patients who were followed up after the MIC diagnosis and those patients who underwent a second treatment directly after the diagnosis without prior control.

Methods

Retrospective study including 144 cases of stage IA1 MIC diagnosed after conization, between 1987 and June 2019.

Results

HPV 16 was the most common genotype.

In the group which received a second treatment directly –without any follow-up visits after conization– 75% underwent hysterectomy and the rest underwent a second conization. Regarding the histological results obtained in those patients, who had a hysterectomy as a second direct treatment, 65% were negative for intraepithelial lesions, 9% were low-grade lesions, 16% high-grade and only 10.5% confirmed invasive carcinoma.

The histological results obtained in those patients who had a re-conization as a second direct treatment were negative in 32%, low grade in 37%, 5% of CIN 2 and malignancy was confirmed in 26%.

There were no negatives cases in the group followed-up prior after the diagnosis. 100% were high-grade lesions in the hysterectomized patients, and 25% of those who were re-conizated. There were not any cases of unnecessary hysterectomy in this group.

Conclusions

The best approach to treat stage IA1 MIC is conization and always scheduling surgical treatment depending, not only on the histological grade obtained after the first treatment, but also taking into account the follow-up visit results.

Our results demonstrated that the hysterectomies performed without a previous visit to study the residual cervix result in histopathology-negative outcomes in 65% of cases.

Therefore, confirmation of the residual disease by evaluating the margin status is essential to make the proper decision regarding the second treatment, because is possible to perform a conservative management in many cases.

Introduction

Data on the long term prognostic value of High Risk (HR)-HPV when added to the margins involvement in the management of CIN2-3 large loop excision of the transformation zone (LLETZ) are scarce. We assess the predictive value of HR-HPV test on the 20 years risk of CIN2-3 among LLETZ-treated women for CIN2–3.

Methods

Retrospective cohort study of 242 consecutive adult women affected by CIN 2-3 and treated by LLETZ at the Department of Gynecology of the Hospital Universitari de Bellvitge (Barcelona, Spain) recruited between January 1996 and September 2006, followed to June 2016. Clinical information and HR-HPV status was recruited from pathological reports. Accuracy of the first cytological and HR-HPV after LLETZ results and margins involvement, alone and combined, was assessed by estimating the sensitivity, specificity, positive and negative predicted values of residual/recurrent CIN2–3. Unconditional logistic regression and Cox proportional hazard models were used to identify the determinants of residual or recurrent CIN 2-3, and failure rates were estimated by Kaplan-Meier analysis.

Results

CIN 2-3 was associated with HR-HPV (Hazard Ratio (HaR)=30.58; 95% Confidence Interval (CI)=3.80-246.20); Age>35 years (HaR=5.53; 95%CI=1.22-25.13); and margins (HaR=7.31; 95%CI=1.60–33.44). HR-HPV showed a sensitivity of 88.8% and a specificity of 80%. Women with ecto(+)/endocervical(+) margins (16.7%), those with uncertain (19.4%) and those with ecto(-)/endocervical(+) margins (9.1%) had higher risk of recurrence (Odds Ratio (OR)=13.20 (95%CI=1.02-170.96), OR=15.84 (95%CI=3.02-83.01), and OR=6.60 (95%CI=0.88-49.53)), respectively. Women with involved margins and/or HR-HPV positive had more treatment failure than those who were HR-HPV negative irrespective of margins or had clear margins (P-log rank<0.001).

Conclusions

HR-HPV and margins are both essential for stratifying post-LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women in order to reduce the risk.

Introduction

Human Papillomavirus (HPV) plays a defining role in the development of cervical cancer. High-risk types of HPV are necessary but not sufficient to develop cervical disease. Previous data has shown a potential role of Epstein-Barr Virus (EBV) as a co-factor to HPV in the development of cervical disease. This study focuses on the predictive ability of detection of both hr-HPV and EBV in the development of disease in a cohort of HIV+ women

Methods

Cervical samples were collected from a cohort of 125 HIV+ women and tested for the presence of high-risk HPV, EBV and Pap smear testing. Cervical biopsies were collected as per clinical guidelines. Demographic characteristics, laboratory data including CD4 cell counts and HIV viral load, and social/behavioral risk factor questionnaires were collected. These women were followed prospectively via electronic medical record

Results

The cohort’s average age was 42.3, mostly (88%) African-American with a mean CD4 cell count of 476 cells/ml and median HIV viral load of 124 copies/ml. High risk HPV was detected in 84% and EBV in 54%. Abnormal Pap smears developed in 46% and 48% had a subsequent cervical biopsy. The presence of EBV and hr-HPV increased the development of future abnormal Pap smears (46% vs 30%, p=.03) as compared to those with hr-HPV only. However, there was no difference in the development of an abnormal cervical biopsy in those shedding both EBV and HPV (59% vs 61%).

Conclusions

The presence of EBV in conjunction with hr-HPV does increase the risk of development of abnormal cervical cytology but not histological lesions. EBV may still be useful as a biomarker for those who will develop early cervical disease prior to histological changes. Future studies will focus on better defining the role of EBV utilizing cervical biopsy tissue.

Introduction

Definitive chemoradiation and radical hysterectomy with pelvic lymph node dissection both are treatment options for FIGO 2018 stage IB3 and IIA2 bulky cervical carcinoma. However, significant acute and late treatment-related toxicities were observed. Induction chemoradiation with simple extrafascial hysterectomy may potentially reduce this toxicity. This study aims to retrospectively assess the outcomes of this multimodality therapy. Besides, residual tumor pattern and morphological change was presented to guide further optimization of brachytherapy.

Methods

Twenty-four patients with FIGO IB3 and 2A2 bulky carcinoma of cervix received planned induction chemoradiation with weekly cisplatin followed by simple extrafascial hysterectomy during 2000-2017 in our institution were identified.

Most patients were squamous cell carcinoma (N=19, 79.2%), followed by adenocarcinoma (N=3, 12.5%), adenosquamous carcinoma (N=1) and poorly differentiated neuroendocrine tumor(N=1).There median age was 51.9 years (range, 40.5-68.7 years) and the median tumor size was 50.3mm (range, 40-95mm).

The EQD2 for high risk clinical target volume defined by GEC-ESTRO guideline was between 50 to 60 Gray(a/b=10) in 93.3% of patients. Surgery was performed 47 days (range, 27-70 days) after completion of chemoradiation.

Results

With a median follow-up of 7.03 years (range, 0.4-15.6 years), 5-year overall survival, local recurrence free survival, and distant metastasis free survival were 91.7%, 91.3%, and 95.8%. 11 of 24 (45.8%) experience pathological complete response (pCR). Two late grade 3 urinary toxicity was observed, one patient experienced local recurrence and one had ureteral injury during operation. Although not statistically significance, patients with pCR and squamous cell carcinoma had better outcome.Treatment effect include cytologic alteration such as cytoplasmic vacuolation and nuclear pleomorphism, as well as stromal changes such as fibrosis with mucin pools at the site of previous tumor.

Conclusions

Induction chemoradiation combined with simple extrafascial hysterectomy in FIGO 1B3 and 2A2 bulky cervical squamous cell cancer is feasible with minimal toxicity and good oncological outcome.

Introduction

Modern cervical screening for high-grade precancerous lesions and cancer is based on cytology and high-risk human papillomavirus (HR-HPV) DNA detection. However, the sensitivity of cervical cytology is limited and strongly influenced by human factors. HPV testing, despite its higher sensitivity, offers a much lower specificity, and, moreover, is misses HPV-negative lesions. Therefore, the search for new biomarker-based cervical screening methods is actual. Here, we evaluated the diagnostic performance of miRNA and mRNA-based molecular classifiers in >600 air-dried smears of patients with underlying cervical lesions of different grade, cancer, or without the disease.

Methods

The air-dried Pap stained cervical smears were collected at four clinical settings. Total nucleic acid extraction, identification, genotyping and viral load assessments of HR-HPV DNA were performed using commercial kits (AO Vector-Best, Russia). The levels of 26 candidate microRNAs and 12 mRNAs were assessed by real-time qPCR. Levels of miR-124 and MAL2 promoter methylation were analyzed by methyl-sensitive PCR.

Results

The concentrations of selected miRNAs and mRNAs changed gradually with the increase of lesion severity. CDKN2A was the best mRNA marker of cervical lesions whereas miR-375 was the best miRNA marker. In general, miRNA-based classifiers were better at discriminating HSIL from LSIL, but mRNA-based classifiers better discriminated HSIL from NILM. The miRNA classifiers generated false-positive results in patients with atrophy and after surgical interventions. The best classifier, based on combined analysis of 3 miRNAs and 3 mRNAs, was more predictive for HSIL than HPV testing at the similar sensitivity. The degree of HSIL risk estimated by combined classifier correlated to MAL2 and miR-124 methylation, but not to the HPV viral load or genotype.

Conclusions

Our results support the feasibility of using cellular biomarker-based methods in cervical screening. This approach could provide advantages over HPV-based triage tests, as it skips the cases of transient HPV infection, and can detect HPV-negative lesions.

Introduction

Cervical carcinoma is the most common malignancy associated with pregnancy. FIGO stage IA1 microinvasive squamous cell carcinoma is usually diagnosed after conization, when maximum depth of 3 mm of invasion and maximum horizontal spread of 7 mm is observed. A treatment with radical surgery was proposed decades ago, however when pregnancy is desired, optimal less invasive treatment is a challenge.

Methods

The case of 33-year-old nulliparous woman referred to Lower Genital Tract Pathology Unit of the Mother-and-Child University Hospital Complex of the Canary Islands with diagnosis of high grade squamous intraepithelial lesion (HSIL) and positive for HPV 16 and others high risk HPV types. A conization was performed and the pathohistological diagnosis was well differentiated squamous cell carcinoma with stromal invasion of 1 mm in depth and positive canal and resection margins. No signs of cancer spreading were present (FIGO IA1).

Results

The first control postconization at 6 months, was low-grade SIL and positive for HPV 16 and others HPV with p16-expression. Five months later, a new test was performed obtaining a negative PAP smear and biopsy but nevertheless persistent HPV-16 infection.

The patient became pregnant from assisted reproduction techniques and delivered a newborn weighing 3450 g at 40+2 weeks.

The follow-up continued in the unit until 2019 when the results of a PAP smears was still negative but HPV-16 infection persisted, then a second conization was indicated. Histological evaluation of the conization specimen showed CIN 3 and negative endocervical canal and margins.

Conclusions

More conservative surgical approaches (conization) to early stages in cervical cancer for young women have been suggested as an appropriated management.

Fertility-conserving surgery is safe for nulliparous young women with stage IA1 cervical carcinoma.

Introduction

FRD ® (Folate Receptor-mediated Detection) has been proposed as a reliable method to screen cervical intraepithelial neoplasia 2+ (CIN2, CIN3, and cervical cancer). This study investigates the clinical significance of FRD ® by comparing the accuracy of FRD ® with that of HPV Testing and Thinprep Cytology (TCT).

Methods

From March 2019 to April 2019, 81 patients in the gynecology clinic of the Second Hospital of Jilin University received screening with FRD ®, TCT, and HPV examinations upon visiting the clinic. If any of the three tests provided a positive result, colposcopy was performed with biopsy being the gold standard for pathological diagnosis.

Results

The sensitivity of FRD ®, TCT, and HPV in the diagnosis of cervical intraepithelial neoplasia 2+ (CIN2, CIN3, Cervical Cancer) were 72.22%, 72.22%, and 83.33% respectively. The specificity of FRD ®, TCT, and HPV in detection of CIN2+ was 65.07%, 60.31%, and 25.39% respectively. The accuracy of FRD ®, TCT, and HPV in diagnosis of CIN2+ was 66.67%, 62.96% and 38.27%. The positive predictive value (PPV) of FRD ®, TCT, and HPV in diagnosis of CIN2+ was 37.14%, 34.21% and 38.27% respectively, while the negative predictive value (NPV) was 89.13%, 88.37% and 84.21% respectively.

Conclusions

FRD ® provided high values of sensitivity, specificity and accuracy. FRD ® has advantages in detection speed (< 60 seconds), economic cost, and patient compliance. FRD ® can be an effective and advantageous tool for the primary screening of cervical intraepithelial neoplasia 2+ (CIN2, CIN3, Cervical Cancer), especially in regions with hard-to-reach patients. FRD ® could also provide significant value as a co-test with HPV Testing.

Introduction

Human papillomavirus (HPV) testing within a screen-and-treat program has the potential to lower mortality from cervical cancer in low-resource settings. We evaluate access to treatment following community-based HPV-testing.

Methods

Women age 25-65 years underwent HPV self-testing at a community health campaign in Western Kenya. HPV-positive women were invited for treatment at neighboring health facilities. We determined the proportion of women successfully accessing treatment and variables associated with successful treatment acquisition.

Results

Among 750 women in the study, 140 (18.6%) tested positive for HPV. One hundred and thirty women were notified of their HPV results, of whom 77 (59.2%) sought treatment, and 73 (52.1%) received cryotherapy. Women who received treatment had a significantly shorter time from screening to result notification [91 days (SD ± 23)] compared to those who did not receive treatment during study follow-up [99 days (SD ± 18), p=0.03]. There was no difference between women who accessed treatment compared to those who did not in respect to age, HIV status, marital status, education level, or history of cervical cancer screening.

Conclusions

Effective cervical cancer prevention programs must link screening to timely and appropriate treatment. In this study evaluating access to treatment among HPV-positive women following a multi-disease community-based campaign in Western Kenya, we found that while treatment with cryotherapy was highly acceptable to women, linkage to treatment was suboptimal, at only 52%, six months after screening. This highlights an urgent need for strategies aimed at strengthening linkage to treatment in similar settings. To support the cost-effectiveness of HPV-based screening, strategies to decrease loss-to-follow-up such as point-of-care diagnostics with same-day treatment, and/or faster time to result notification, and use of patient navigators to promote adherence to follow-up need further investigation.

Introduction

Human Papillomavirus (HPV) is a necessary cause of cervical cancer (CC) in which 80% of the disease burden occurs in developing countries where organized screening programmes are not available and, as such, still opportunistic. This study aims to review the opportunistic screening methods used in our centre, and the treatment methods offered for high grade abnormalities.

Methods

A ten-year review (January 2009- December 2018) was carried out on records of patients that had opportunistic screening for CC in our centre. The methods of diagnosis, histological results, treatment methods and follow up of these patients were recorded.

Results

A total of 11,597 clients had cervical cancer screening during the study period. In 18% of cases, pap smear was done using liquid-based cytology and 72% using conventional cytology. A total of 98 smears were inadequate, more with the conventional (89%). Immunohistochemistry for P16/Ki67 was not routinely done, except for research purposes. No single case of high risk HPV deoxyribonucleic acid testing (hrHPVDNA) or visual inspection was done. The histology result showed CIN II/III or HSIL on cytology in 8.6%, CINI or LSIL in 5.6%, negative/inflammatory in 79% and atrophic in <1%. Ninety-two percent had colposcopy and biopsy after diagnosis of HSIL with an 83 percent concordance of cytology and histology. Of these, 70 (76.9%) had hysterectomy, 11 (12.1%) had cone biopsy, and 9 (9.9%) had cryotherapy. One client had no treatment at all / no treatment record was seen. No client had loop electrosurgical excision procedure (LEEP). Treatment method largely depended on fertility desire, availability of treatment options, and coexisting pathologies. There was no defined follow up pattern for these clients.

Conclusions

The availability of organized screening using HPVDNA testing and treatment using LEEP excision in resource poor settings will go a long way in reducing the burden of cervical cancer.

Introduction

Current clinical standard usually requires histologic confirmation of precancer before treatment. We investigated if persistent HPV in women aged 18-39 without prior biopsy confirmation yields similar rates of underlying precancer as those with prior biopsy confirmation, as a potential clinical indicator for LEEP.

Methods

In the Costa Rica Vaccine Trial, 7466 women were randomized to HPV or control vaccine and followed annually 4 years. HPV-vaccinated participants were invited to long-term follow-up (LTFU) for 6 more years at two-year intervals. Additionally, 2,836 unvaccinated women from the same areas and cohorts were enrolled as a new control group. All women were followed with cytology and HPV tests. When screening resulted in biopsy confirmed cervical precancer; women were offered LEEP. In the absence of biopsy confirmation, after discussion of individual cases, we performed diagnostic LEEPs on women with persistent HPV infection or high-grade colposcopy impression. Here, we included all women with a LEEP regardless of the indication (histologic CIN2+, persistent HPV infection, other [i.e. high-grade cytology or colposcopy]), and compared the percentage of women with CIN2+ on the diagnostic LEEP specimen to therapeutic LEEP (i.e. biopsy-confirmed). We further estimated disease recurrence post-LEEP.

Results

47.5% of those with LEEP had CIN2+, regardless of preceding biopsy suggesting CIN2+ (46.5%,), persistent infection without evidence of HSIL/CIN2+ (54.3%;), or other reasons (45.0%;). Among diagnostic LEEPs in women with persistent HPV, the proportion with underlying precancer was significantly higher for women with persistent HPV16/18/45 compared to persistent non-HPV16/18/45 (75.5% vs 36.5%; p=<0.0001) regardless of presence of histologically confirmed CIN2+. Recurrence after LEEP was low in all groups (Table).

Conclusions

In the absence of histologic confirmation of high-grade disease, our data support diagnostic LEEP in the presence of persistent HPV infection, particularly for HPV 16/18/45 infections. LEEP remains a highly effective treatment with low recurrence.

Introduction

Cervical cancer is exceedingly rare in adolescents. In 2009, U.S. guidelines discouraged screening in young immunocompetent women <21 years of age. This study aims to ascertain the trends and factors associated with unindicated screening in adolescents.

Methods

Cervical cancer screening tests performed in females <21 years from 2012–2018 were reviewed from Yale New Haven Health System. The final diagnosis, the results of HPV testing, and the clinical indications for the procedure were extracted using Natural Language Processing. Each screening test was adjudicated as either indicated or unindicated based on the logic presented in the guidelines. The biannual rate of unindicated screening was calculated as the ratio of unindicated cases to the total number of <21 years patient visits completed by a given provider during a 6-month interval for the overall sample, for each practice setting, and for provider degrees.

Results

Data from 118 providers and 797 women (N=906 Paps) were included. Characteristics of patients are detailed in Table 1. The reasoning for performing screening was not given for 62% of the reports. The most common reasons listed were “routine clinical care” (63%) or “history of prior cervical abnormalities” (23%). Although most adolescents had an unindicated pap, 8% had a follow-up pap after receiving an abnormal result on a prior unindicated pap. During the study period, 49 colposcopies and 3 conizations were performed in women <21 years. Although the incidence of unindicated screening was more than twice as high among community-based providers, the rate of reduction was greater in the community than in the academic setting during the study period (Table 2).

Conclusions

Nearly a decade has passed since the release of the current cervical cancer screening guidelines in the US, yet unindicated screening of adolescents remains a challenge. More research is needed to identify better strategies to reduce the overutilization of screening.

Introduction

Invasive cervical cancer is preventable, yet affects 500,000 women worldwide each year, and over half these women die. Barriers to cervical cancer screening include lack of awareness of cervical cancer and the cervix, fear of the speculum and lack of women-centric technologies. We developed a low-cost (~$50), cervix-imaging device called the Callascope, which comprises an imaging component, camera, and inserter which obviates the need for a speculum and enables self-insertion. Studies are lacking regarding women’s willingness to independently image their cervix and women’s ability to effectively use the Callascope for self-imaging.

Methods

We conducted two studies: (1) in-depth interviews to assess willingness to self-image the cervix, perceptions of the Callascope, and knowledge, attitudes, and practices (KAP) towards cervical cancer screening, and (2) home-based self-cervix imaging with the Callascope where women recorded an audio-reflection on their experience.

Results

Participants of the interviews (n=12) and home study (n=12) all indicated a preference for the Callascope over the speculum. Interview data showed that 53% of participants had little knowledge of basic reproductive anatomy, and only 17% of participants understood that HPV was a direct cause of cervical cancer. Self-exam data showed that 83% of participants were able to visualize their cervix with the Callascope on the first try and 100% by the end of the study. 100% of participants indicated that the home-exam was an empowering and informative experience.

Conclusions

The Callascope is more comfortable than the speculum and women are able to successfully image their cervices from home without the need for a speculum. With improved diagnostic capabilities, the Callascope could be used by medical providers for clinical exams, particularly in low-resource settings, as a low-cost and more comfortable alternative to the SOC. The Callascope enables home self-screening for cervical cancer and a better understanding of one’s body, which could make screening more accessible in low-resource settings.

Introduction

About 10% of IVCC cases were positive with multiple HPV types, and about 5% of cancer were not detected any HPV types in our previous study. To determine a single HPV type responsible for cancer development, we used a new procedure.

Methods

Nine IVCC cases having multiple HPV types and 8 IVCC cases which not detected any HPV types by the previous assay were investigated. Formalin fixed and paraffin embedded were cut out by laser captured microdissection. HPV genotyping were determined using the uniplex E6/E7 PCR method able to detect E6 or E7 DNA of 39 HPV types.

Results

Among 9 cases of multiple HPV type infection, 4 cases were positive with HPV-16, 3 cases with HPV-18, and each one case was HPV-67 and -59. Among 8 cases not detected HPV, HPV-16 was found in 2 cases, HPV-18 and -67 were in each one case, and 2 cases were negative. The negative cases were 2 adenocarcinoma (ADC) and one minimal deviation adenocarcinoma and large cell neuroendocrine carcinoma. One adenosquamous carcinoma (ADSQC) with HPV-52 and one SCC with HPV-51 were examined, and HPV-18 and HPV-16 were identified. HPV-52 was positive in squamous cell area covering ADSQC tumor in the first case, and HPV-51 was detected in the vagina of the second case.

In 17 cases, HPV-16 was in 6 cases (4 SCC, one ADC, one small cell neuroendocrine carcinoma), HPV-18 in 4 cases (one SCC, 2 ADC, one ADSQC), HPV-67 in 2 SCC, and HPV-59 in one ADC were identified.

Conclusions

HPV genotyping using tissue microdissection procedure with the uniplex E6/E7 PCR is the most powerful tool to identify HPV genotype in cancer specimen. HPV-67 is likely to be high-risk type, since it was identified in 2 SCC cases who have died for the cancer.

Introduction

Sensitive, molecular high-risk HPV (HR-HPV) tests for early detection of cervical precancerous lesions are now in wide-spread use in many high-income countries. However, screening and prevention programs in low- and middle-income countries (LMICs) suffer from major cost and infrastructure constraints, poor participation, loss to follow-up, and concerns about sustainability. If an accurate, inexpensive, and simple technology of HR-HPV testing can be used with self collected vaginal samples, screening and prevention programs in LMICs may be greatly improved.

Objective: To demonstrate transporting a dry brush vaginal sample is an accurate transport method to detect HR-HPV.

Methods

500 women are currently being recruited between the ages of 30-55 from outpatient and colposcopy clinic. Three samples are being collected by doctor from each patient. The first sample was “pseudo self –collected sample” from the vagina before placing vaginal speculum. The brush was placed in an empty collection bottle. Two other brush samples were obtained directly from the endocervix after placement of speculum. One brush was placed into an empty collection bottle and the other placed in 2ml liquid Ampfire transport media. All samples are being analyzed by Ampfire HR-HPV assay which has the ability to accept raw sample. McNemar Chi-square statistic was used for analysis.

Results

The first 197 patient samples have been analyzed. Percent HPV positives for vaginal dry, cervix dry, and cervix liquid, were 44.7%, 47.2%, 43% respectively. There was no significant difference in detection rate for HR-HPV of the dry vaginal sample compared to the direct endocervical liquid sample (P=0.664), or the direct dry brush sample (P=0.302).

Conclusions

The full data set will be reported. However, if the above trend continues the dry brush transport could markedly simplify and reduce costs for specimen transport. Used with self-collected vaginal samples, it may become an important addition to population based cervical cancer screening programs.

Introduction

The cancer of the cervix especially remains true public health problems in the developing countries. It constitutes the 4th cancer at the woman in the world; whereas it occupies the 2nd position in the developing countries, especially in south sahara Africa .

Methods

: Our study proceeded in all the health systems of the district

Bamako of the first January 2010 at December 31st, 2017 (8ans). It was about a retro study prospective and descriptive.

Results

For the study period we detected 121904 women by test IVA and or IVL whose 8016 biopsies is 6,57% of the detected women. The average age is 34,23 years with extremes from 14 to 100 years

We then have a total frequency of 2,55% for the precancerous lesions that of the cancerous lesions is 1,05%. We carried out the cryotherapy (09.6%), RAD (12%), Hysterectomy (1%)

Conclusions

The assumption of responsibility of the lesions can reduce considerably the burdens of cancer in the developing countries.

Introduction

HPV is identified in almost all squamous invasive cervical carcinomas and a high proportion of adenocarcinomas. HPV involvement in cervical adenocarcinoma is between 8.3% - 71.8% depending on the histological subtype. A new morphological classification of adenocarcinomas has been proposed where ADC are classified based on the presence or absence of HPV infection-related features (IECC, International Endocervical Adenocarcinoma Criteria and Classification, 2017). Two adenocarcinoma groups were established: HPV-associated (HPVA) and non-HPV associated (NHPVA).

The objective is to evaluate the reproducibility of IECC morphological criteria with a highly sensitive HPV testing in our own series of cervical adenocarcinomas.

Methods

We identified sixty-nine incident cases of endocervical adenocarcinoma identified through Tarragona and Girona cancer registries (Catalonia) between 1998-2007. All adenocarcinoma hematoxylin and eosin (HE) slides were reviewed by two expert pathologists and classified in accordance with the IECC system. HPV DNA was done using SPF-10 PCR/DEIA/LiPA25. Demographic and clinical information was retrieved from the cancer registry databases.

Results

The morphological diagnostic distribution was; HPVA (n=51): usual -type (56.5%), mucinous, not otherwise specified (10.1%); villoglandular (4.3%), mucinous, intestinal type (2.9%); NHPVA (n=18): clear cell adenocarcinoma (8.7%), gastric-type adenocarcinoma (7.2%), endometroid adenocarcinoma (5.8%), serous adenocarcinoma (2.9%) and mesonephric carcinoma (1.4%). The mean patient’s age in HPVA was 50.4, compared to 55.4 in NHPVA (p>0.05). HPV was identified in 68.6% of HPVA tumors and in 5.6% of NHPVA tumors (p<0.05). Tumor stage IV at diagnosis was 7.8% in HPVA and 16.7% in NHPVA (p>0.05). Finally, 27.5% of HPVA patients dead by cervical cancer compared to 33.3% of NHPVA (p>0.05).

Conclusions

Our results using IECC criteria with HE are supported by HPV detection results. The use of a specific immuno-marker p16, and HPV detection would help in complex diagnosis.