Cervical cancer screening in HIV-endemic countries: An urgent call for guideline change.

Women living with HIV (WLWH) are at an increased risk of developing HPV-related high grade cervical dysplasia and cervical cancer. Prior World Health Organization (WHO) screening guidelines recommended starting screening at age 30. We assessed characteristics of women diagnosed with cervical cancer to further inform and refine screening guidelines. We prospectively enrolled women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. We performed chi-square and ANOVA analyses to evaluate the association between age upon diagnosis and HIV status, CD4 count, viral load, and other sociodemographic and clinical factors. Data were available for 1130 women who were diagnosed with cervical cancer and 69.3% were WLWH. The median age overall was 47.9 (IQR 41.2-59.1), 44.6 IQR: 39.8 - 50.9) among WLWH, and 61.2 (IQR 48.6-69.3) among women living without HIV. There were 1.3% of women aged <30 years old, 19.1% were 30-39 and 37.2% were 40-49. Overall, 20.4% (n = 231) of cancers were in women <40 years. Age of cervical cancer diagnosis is younger in countries with higher HIV prevalence, like Botswana. Approximately 20% of the patients presented with cancer at <40 years of age and would have likely benefited from screening 10 years prior to cancer diagnosis to provide an opportunity for detection and treatment of pre-invasive disease.

Prevalence of precancerous cervical lesions and high-risk human papillomavirus types in Yaounde, Cameroon.

INTRODUCTION: Various Human papillomavirus (HPV) types cause cervical cancer, and represent the primary cause of cancer death in Africa and the second cause of most common cancers in Cameroon. Herein, we determined the prevalence of high-risk HPV types in women and associated cervical cytologic abnormalities in Yaounde, Cameroon. METHODOLOGY: A cross-sectional study targeting HPV-positive women aged 20 and over was conducted between March and June 2020 at the Saint Martin de Porres' Health Centre in Yaounde. HPV tests were performed by PCR for detection of HPVs 16, 18, 33, and 45. The test was performed on 616 women using exfoliated cell specimens; then, we processed on cytological diagnosis with Pap smears on HPV positive specimens. RESULTS: The HPV types tested were detected in 137 participants, of which 38.7% with multiple HPV infections, and the remaining part with single HPV infections of type HPV 16 (28.5%), HPV 18 (17.5%), HPV 33 (10.2%), and HPV 45 (5.1%). Cervical cytologic abnormalities were found in 69.34% of participants including: LSIL (49.63%), HSIL (15.32%), ASC-US (3.66%) and AGC (0.73%). Co-infections with HPV 16 and HPV 18 were significantly associated with HSIL (p = 0.001) lesions, while HPV 45 was more common in participants with normal cytology (p = 0.001). Cervical lesion occurrence was significantly associated with the number of sexual partners (p = 0.02) and history of oral contraceptive pill use (p = 0.001). CONCLUSIONS: Our results suggest that HPV 16 and 18 are predominant in Yaounde, and are associated with more severe precancerous lesions.

Human Papillomavirus Testing in the Last Cervical Screening Round at Age 60-64 Years.

OBJECTIVE: To compare the real-life screening outcomes after cytology was replaced by human papillomavirus (HPV) testing for women aged 60-64 years. METHODS: Using the Danish national pathology register, we compared screening outcomes during two consecutive calendar periods, one where women were screened with cytology and one where most women were screened with HPV testing. Our primary outcomes were the proportions of women with positive test results, high-grade cervical intraepithelial neoplasia (CIN 2 or worse), and cervical cancer. RESULTS: Women screened during the HPV testing period were more likely to have a positive screening test result than were women screened during the cytology period (relative proportion 2.80, 95% CI 2.65-2.96). The detection of CIN 2 or worse was also increased (relative proportion 1.54, 95% CI 1.31-1.80), whereas there was no increase in screen-detected cervical cancer diagnoses (relative proportion 1.27, 95% CI 0.76-2.12). Within the first 4 years after a negative screening test result, including 168,477 woman-years at risk after a negative screen result in the HPV period and 451,421 woman-years after a negative screen result in the cytology period, the risk of a cervical cancer diagnosis was approximately 4 per 100,000 woman-years and was similar for both screening tests (relative risk 0.99, 95% CI 0.41-2.35). CONCLUSION: Human papillomavirus testing led to more positive screening test results and diagnoses of high-grade CIN lesions. Few women were diagnosed with cervical cancer after a negative screening test result.

Relationship between polymorphisms in the FAS/FASL death receptor system and progression of low-grade precursor lesions infected with high-risk human papilloma virus.

Squamous intraepithelial lesions (SIL) and cervical cancer are primary due to suboptimal immune response against human papillomavirus (HPV). The FASL/FAS system is a trigger of extrinsic pathway apoptosis. The distribution of polymorphisms rs1800682 (-670 A > G) FAS and rs763110 (-844C > T) FASL was studied in cervical smears from 372 females (182 with stable or regressed low-grade SIL (LSIL) (groupI) and a group of 190 high-grade SIL (HSIL) (groupII). No significant differences were observed for rs1800682 in FAS between the study groups. In contrast, rs763110 CC genotype of FASL was found in 35.7% of group I females, and in 50.5% of group II (p = 0.0027; OR = 1.83 (95% CI = 1.21-2.79)). When only females infected with high-risk HPV were analysed, these differences were even higher (p = 0.0024; OR = 2.21 (95% CI = 1.30-3.75)). CC genotype in FASL seems to be associated with increased risk of LSIL to HSIL progression suggesting a role in HPV tolerance, persistent infection, and HSIL development.

Is stress related to the presence and persistence of oncogenic human papillomavirus infection in young women?

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for the development of cervical cancer, but factors contributing to HR-HPV persistence are incompletely understood. The objective of this study was to test for associations of chronic stress and two aspects of diurnal cortisol secretion (i.e., the cortisol awakening response [CAR] and total cortisol output over the day [AUCgday]) with HR-HPV status at baseline and 12 months later (follow-up). METHODS: We evaluated 188 women (25 ± 3 years) at baseline. Follow-up investigation was restricted to HR-HPV infected women at baseline. Of the initial 48 HR-HPV positive participants, 42 completed the follow-up (16 HR-HPV positive and 26 HR-HPV negative). At baseline and follow-up, we determined HR-HPV status in cervical smears, assessed chronic stress, and repeatedly measured salivary cortisol over the day. At baseline, we analyzed salivary cortisol only in a subgroup of 90 participants (45 HR-HPV negative and 45 HR-HPV positive). RESULTS: At baseline, higher chronic stress (excessive demands at work: p = .022, chronic worrying: p = .032), and a higher CAR (p = .014) were related to baseline HR-HPV positivity. At follow-up, there was a statistical trend for a positive association between the CAR and HR-HPV positivity (p = .062). Neither the CAR nor the AUCgday mediated the associations between chronic stress and HR-HPV status. CONCLUSIONS: Our findings suggest that both chronic stress and diurnal cortisol are related to the presence of HR-HPV infection and may thus play a role in HPV-associated cervical carcinogenesis.

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions.

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.

Is smoking an independent risk factor for developing cervical intra-epithelial neoplasia and cervical cancer? A systematic review and meta-analysis.

Introduction: Cervical cancer is the fourth most common form of cancer among women. Smoking tobacco seems to be a risk factor for the development of cervical intra-epithelial neoplasia (CIN) and cervical cancer, but the exact role of smoking in the process of cervical carcinogenesis is not known. The aim of this study is to investigate the relationship between smoking and the development of CIN and cervical cancer. Areas covered: We searched Embase, Medline, Cochrane Central, Web of Science, and Google Scholar for studies on smoking and CIN and cervical cancer, published between 2009 and 2018. The following were the outcomes: CIN3 alone, CIN2 and CIN3 combined, CIN2+, CIN3+, and cervical cancer alone. We included 49 studies in our review and 45 in our meta-analyses. Expert opinion: Based on the available evidence it can be - cautiously - concluded that smoking increases the risk of cervical abnormalities. However, the high risk of bias indicates that for future studies, it will be important to adjust for relevant predictors, to separate CIN from cervical cancer as outcome measures, and to report research methods in detail.

Risk of Cervical Intraepithelial Neoplasia Grade 3 or Worse in HPV-Positive Women with Normal Cytology and Five-Year Type Concordance: A Randomized Comparison.

BACKGROUND: In human papillomavirus (HPV)-based cervical screening programs, management of HPV-positive women with normal cytology is debated. Longitudinal information on HPV type persistence may be employed for risk stratification. METHODS: We assessed the risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) after repeatedly testing positive for the same HPV type(s) in the randomized population-based screening study Amsterdam (POBASCAM). We compared 18-month CIN3+ risks in HPV-positive women (intervention, n = 1,066) to those in HPV-positive/cytology-negative women who tested HPV-positive in the next screening round (control, n = 111) five years later, stratified for HPV type concordance. RESULTS: The 18-month CIN3+ risk was 15% in HPV-positive women in the intervention group, 40% in the control group after two-round type concordance (relative risk 2.6, 95% confidence interval 1.9-3.4), and 20% in the control group after a type switch (1.3, 0.5-3.2). The relative increase in CIN3+ risk after two-round type concordance was similar in <35-year-old (3.0, 2.0-4.4) and older women (2.2, 1.4-3.5), and was high in high-risk HPV-positive women who were HPV16/18/31/33/45-negative in both rounds (9.9, 4.4-21.9). CONCLUSIONS: Five-year HPV type concordance signals high CIN3+ risk and warrants referral for colposcopy without additional cytology triage. IMPACT: HPV screening programs become highly efficient when HPV-positive women with negative triage testing at baseline are offered repeat HPV genotyping after five years.

Cervical dysplasia in a patient with inherited epidermodysplasia verruciformis-A mere coincidence?

Epidermodysplasia verruciformis (EV) is a rare inherited or acquired genodermatosis caused by increased susceptibility to infection by the beta subtypes of human papillomavirus (HPV). The co-occurrence of EV with high-risk (HR) HPV infection leading to cervical dysplasia is unreported in the literature to date. We report a patient with inherited EV who developed extensive anogenital and cervical dysplasia linked to concurrent HR-HPV infection. Literature review suggests that there is a negative correlation of cervical dysplasia and cervical cancer with EV, which suggests that this patient's presentation and course are exceptional.

Correlation of High-Risk HPV Genotypes with Pap Test Findings: A Retrospective Study in Eastern Province, Saudi Arabia.

INTRODUCTION: High-risk human papillomavirus (HR HPV) is found to be responsible for 4.5% of cancer in general, primarily cervical cancer. We aim here to highlight the prevalence and genotypes of HR HPV and correlate its association with Pap tests' results, which are still not well known in the Eastern Province of Saudi Arabia. METHODS: Over 7 years (2013-2019), the results of 164 Saudi women coinvestigated for HR HPV along with Pap tests were collected from the archive of King Fahd University Hospital. Only women who had atypical squamous cells of undetermined significance (ASCUS) on the Pap test and those at elevated risk of infection were cotested for HR HPV; otherwise, the Pap test was the only screening modality for cervical cancer. Data were organized and statistically analyzed using IBM SPSS v26. RESULTS: Out of 164 Saudi women, 14.5% (n = 24/164) showed positive results for HR HPV (8 patients had HPV16 and 2 had both HPV16 and HPV18/45, while the remaining 14 had other HR HPV); among them, 41.5% (n = 10/24) had an abnormal Pap test (5 ASCUS and 5 LSIL), while 58.5% (n = 14/24) had a negative Pap test. On the other hand, 21% (n = 35/164) of patients, in the study, had an abnormal Pap test (24 ASCUS, 8 low-grade squamous intraepithelial lesion [LSIL], and 3 atypical glandular cell [AGC]). In 80% (n = 19/24) of ASCUS cases, HR HPV was not detected; however, 20% (n = 5/24) were positive for other HR HPV. Concerning LSIL cases, 62.5% (n = 5/8) were positive for HR HPV (1 case showed HPV16 and HPV18/45, 2 cases showed HPV16, and 2 cases showed other HR HPV), while in the remaining 37.5% (n = 3/8) LSIL cases, HR HPV was negative; similarly, all AGC cases were negative for HR HPV. Statistical analysis showed a significant correlation between HPV status and Pap test findings (p value <0.001). DISCUSSION/CONCLUSION: HR HPV frequency and genotype distribution, in this study, might reflect a different regional infection pattern. The high association of HR HPV with negative cytology emphasizes the need to add the HR HPV test to screening modalities of cervix cancer.

Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2.

BACKGROUND: The vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables. METHODS: In total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software. RESULTS: K-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036). CONCLUSIONS: The vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.

Prevalence and predictors of precancerous cervical lesions among HIV-positive women in Jos, north-central Nigeria.

OBJECTIVE: To determine the prevalence and predictors of precancerous cervical lesions among HIV-positive women in Jos, Nigeria. METHODS: A cross-sectional study was conducted from October 2017 to January 2018 among 326 HIV-positive women. Cervical smears were collected for examination at the AIDS Preventive Initiative of Nigeria clinics of Jos University Teaching Hospital (JUTH) and Bingham University Teaching Hospital (BhUTH), Jos, Nigeria. Demographic characteristics of participants were documented using a structured questionnaire. Data were entered and analyzed using SPSS version 21. RESULTS: Of the 326 participants, precancerous cervical lesions were present in 40 (12.2%) women: 4 (1.2%) had atypical squamous cells of undetermined significance, 19 (5.8%) had low-grade squamous intraepithelial lesions, 1 (0.3%) had atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions, 13 (4.0%) had high-grade squamous intraepithelial lesions, and 3 (0.9%) had high-grade squamous intraepithelial lesions, suspected for invasion. The multivariate logistics regression model showed that parity (odds ratio 3.4, 95% confidence interval 1.3-9.5, P=0.043) was a significant predictor of precancerous cervical lesions. CONCLUSION: The prevalence of precancerous cervical lesions among HIV-infected women is relatively low compared to earlier reported prevalence in an HIV population in Jos. Increasing parity was a significant predictor.

Comparison of HPV Testing and Colposcopy in Detecting Cervical Dysplasia in Patients With Cytological Abnormalities.

AIM: The aim of the study was to compare the diagnostic value of HPV testing and colposcopy in patients with abnormal cytology results. PATIENTS AND METHODS: A total of 186 women with cytological abnormalities were included in the study. The patients underwent colposcopy examinations and DNA HPV testing of cervical smear with genotyping. RESULTS: The HPV test was demonstrated to be more sensitive (79.4%) than specific (60.2%) and was more sensitive than colposcopy for detecting CIN changes (79.4% vs. 73.7%). Combined tests achieved a high sensitivity (90.9%) and negative predictive value (96.1%) in detecting patients with CIN2+ and demonstrated the highest positive predictive value (77.3%) for detecting CIN1+. Colposcopy had a very good specificity (83.5%) and positive predictive value (71.2%) in finding CIN1+ cases. CONCLUSION: HPV tests showed a higher sensitivity than colposcopy, but colposcopy results presented higher specificity. Combining HPV testing and colposcopy proved to be the most efficient method for detecting CIN lesions.

Incidence of HPV and HPV related dysplasia in elderly women in Sweden.

BACKGROUND: About one-third of the cervical cancer cases in Sweden occur in women over the age of 60. The primary aim of this study was to analyze the incidence of HPV, and HPV related dysplasia, in elderly women who had an HPV negative test at the age of 60 years or older. METHODS: From October 2004 to June 2019, 1784 women aged 60-90 years were sampled for an HPV test when attending an outpatient gynecology clinic. Of these women, 827 HPV-negative women had two or more HPV tests at intervals of three months to eleven years (mean 3.2 years). The women with positive results had a repeat HPV test and cytology after 2.5 months on average. Those with a positive repeat HPV test were examined by colposcopy and biopsy. FINDINGS: The overall prevalence of HPV was 5.4%, (95%CI 4.4-6.6, 96/1784). The incidence of HPV in the 827 women, who were HPV negative in their first test, was 2.4% (95%CI 1.5-3.8, n = 20). At the repeat test 1.2% remained positive (95%CI 0.6-2.3, n = 10). HPV-related dysplasia diagnosed by histology was found in 1.2% (95%CI 0.6-2.3, n = 10) of the 827 women. CIN2+ was found in 0.5% (95%CI 0.2-1.3, n = 4). In the repeat HPV test 52.6% 10/19) were HPV positive. The time between an HPV negative test and an HPV positive test and CIN2+ was on average 45.5 months (range 10-85 months). The positive predictive value (PPV) for CIN2+ was 20.0% in the first positive HPV test and 40.0% in the repeat HPV test. The women with CIN2+ had normal cytology. No cancer or glandular dysplasia was detected. INTERPRETATION: In this study older HPV-negative women were at risk of becoming HPV positive. Among the women who were HPV positive in a repeat test, there was a high risk of dysplasia.

MICA and KLRK1 genes and their impact in cervical intraepithelial neoplasia development in the southern Brazilian population.

Cervical carcinoma and cervical intraepithelial neoplasia (CIN) are associated with persistent infection by oncogenic subtypes of HPV (Human Papillomavirus). Factors linked to immunity, genetics and others like oral contraceptive use, sexual behavior, coinfections with other microorganisms and smoking seem to influence the mechanisms that determine regression or progression to CIN and cervical cancer. We investigated the effect of the MHC class I chain-related gene A (MICA) and Killer Cell Lectin Like receptor K1 (KLRK1) genes on cervical cancer and CIN lesions susceptibility in a group of 195 patients from southern Brazil. There were found a significantly higher number of ex-smokers in the control group (p = 0.005). There were more oral contraceptives (OC) users in the patient group. MICA*008:01/04 allele showed a significant difference between patient and control groups (p = 0.03; OR = 0.63, 95% CI 0.41-0.96), as well as MICA*018:01(p = 0.004, OR = 0.15, 95% CI 0.03-0.64) and MICA*002:01/020 (p = 0.01; OR = 0.60, 95% CI 0.40-0.88). We also analyzed cases and controls according to the MICA-129 genotypes (Met/Val). There was found a difference (p = 0.02) with the Met/Val genotype in a higher frequency in controls and Val/Val and Val/MICA del at a higher frequency in the patient group. For the KLRK1 gene there was no significant difference between groups.

Effects of exposure to polycyclic aromatic hydrocarbons combined with high-risk human papillomavirus infection on cervical intraepithelial neoplasia: A population study in Shanxi Province, China.

High-risk human papillomavirus (HR-HPV) infection is a major etiological agent in the progression of cervical intraepithelial neoplasia (CIN) and cervical cancer. Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic pollutants that exist widely in the environment. We hypothesized that PAHs exposure was related to the progression of cervical cancer, and could increase the effect of HR-HPV on CIN. We investigated the effects of PAHs exposure combined with HR-HPV infection on CIN in community population in Shanxi Province, China. A total of 2,285 women were enrolled into the study. HR-HPV genotypes were detected by flow-through hybridization technology. 1-hydroxypyrene (1-OHP) was detected by high-performance liquid chromatography. The top three HR-HPV genotypes were 16, 58 and 52 in turn. With unconditional logistic regression analysis, we found that HR-HPV infection (adjusted odds ratio [aOR] = 4.08, 95% confidence interval [CI]: 3.00-5.54), HPV16 infection (aOR = 4.71, 95% CI: 3.39-6.53), HPV58 infection (aOR = 2.29, 95% CI: 1.41-3.73) and PAHs high exposure (aOR = 2.57, 95% CI: 1.82-3.62) increased the risk of CIN2/3, showing an increasing trend (p < 0.001) with the severity of cervical lesions. Compared to Q1 (<0.06 µmol/molCr) levels of 1-OHP, women with Q4 (>0.11 µmol/molCr) had a higher risk for CIN2/3 (aOR = 7.68, 95% CI: 4.83-12.22). Additionally, we observed that there was a synergic effect between high exposure to PAHs and HR-HPV infection in CIN2/3. Furthermore, the results from the generalized multifactor dimensionality reduction model showed that there were joint interactions of PAHs, HPV16, HPV58 and HPV52 on the risk of CIN2/3. Our study revealed that high exposure to PAHs could increase the risk for CIN, and it posed stronger risk when combined with HR-HPV infection.

Disease detection at the 48-month exit round of the HPV FOCAL cervical cancer screening trial in women per-protocol eligible for routine screening.

HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high-risk human papillomavirus (HPV) and the control arm received liquid-based cytology (LBC) at baseline and 24 months. Both arms received 48-month exit HPV and LBC cotesting. Exit results are presented for per-protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow-up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25-65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56-1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43-1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14-65) and intervention 43 (95% CI: 25-73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1-0.7). This per-protocol analysis found that screening with HPV using a 4-year interval is as safe as LBC with a 2-year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.

Risk of vaginal cancer among hysterectomised women with cervical intraepithelial neoplasia: a population-based national cohort study.

OBJECTIVE: To study the risk of vaginal cancer among hysterectomised women with and without cervical intraepithelial neoplasia (CIN). DESIGN: Population-based national cohort study. SETTING AND POPULATION: All Swedish women, 5 million in total, aged 20 and up, 1987-2011 using national registries. METHODS: The study cohort was subdivided into four exposure groups: hysterectomised with no previous history of CIN3 and without prevalent CIN at hysterectomy; hysterectomised with a history of CIN3/adenocarcinoma in situ (AIS); hysterectomised with prevalent CIN at hysterectomy; non-hysterectomised. MAIN OUTCOME MEASURE: Vaginal cancer. RESULTS: We identified 898 incident cases of vaginal cancer. Women with prevalent CIN at hysterectomy and those with a history of CIN3/AIS had incidence rates (IR) of vaginal cancer of 51.3 (95% CI 34.4-76.5) and 17.1 (95% CI 12.5-23.4) per 100 000, respectively. Age-adjusted IR-ratios (IRRs) compared with hysterectomised women with benign cervical history were 21.0 (95% CI 13.4-32.9) and 5.81 (95% CI 4.00-8.43), respectively. IR for non-hysterectomised women was 0.87 (95% CI 0.81-0.93) and IRR was 0.37 (95% CI 0.30-0.46). In hysterectomised women with prevalent CIN, the IR remained high after 15 years of follow up: 65.7 (95% CI 21.2-203.6). CONCLUSIONS: Our findings suggest that hysterectomised women with prevalent CIN at surgery should be offered surveillance. Hysterectomised women without the studied risk factors have a more than doubled risk of contracting vaginal cancer compared with non-hysterectomised women in the general population. Still, the incidence rate does not justify screening. TWEETABLE ABSTRACT: High risk of contracting vaginal cancer among hysterectomised women having prevalent CIN at surgery.