Colposcopy performance in the new primary HPV screening in Australia: How to determine colposcopy competency?

AIMS: To assess colposcopic performance and determine indicators for competency within the new Australian primary human papillomavirus (HPV) cervical screening program. MATERIALS AND METHODS: A retrospective observational study of 4542 women seen at The Royal Women's Hospital Colposcopy Clinic in Melbourne, from 1 December 2017 to 31 July 2020 after a higher-risk cervical screening test (CST) result. RESULTS: Histological CIN2+ was detected in 25.1% up to two years from first colposcopy visit (FCV). The majority (86.7%) of CIN2+ was detected early within the first six months of presentation. Biopsy rate overall was 96.1% with abnormal colposcopic impression. Of four colposcopists with a lower biopsy rate, only one was able to achieve this early detection rate. Biopsy was also taken in over 30% of cases with negative reflex cytology and normal colposcopy, with CIN2+ detected in 5.0% among positive HPV16/18 and 3.8% with non-16/18 HPV. Positive predictive value of high-grade colposcopic impression at FCV averaged 66.4% (range: 54.9-81.6% among our colposcopists) and is poorly correlated with early detection rate of CIN2+. Overall accuracy of colposcopy is 84.5% (range: 78.7-90.3%), buoyed by high true negative colposcopic predictions secondary to high rates of negative reflex cytology referral with the new screening algorithm and is also unlikely to be a useful colposcopy indicator. CONCLUSIONS: Early detection rate of CIN2+ within the first six months of presentation is a useful measure of colposcopy competency and we would encourage our National Cancer Screening Register to explore this with the participating colposcopists.

Primary HPV cervical screening: Clinical audit of outcomes of women seen at a tertiary referral centre for colposcopy in Australia.

BACKGROUND: Primary human papillomavirus (HPV) screening was introduced in Australia in December 2017. AIMS: Outcomes for women after positive HPV in their cervical screening test (CST). MATERIALS AND METHODS: A retrospective observational study of 4458 women seen at the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. RESULTS: HPV16/18 was positive (considered higher-risk CST) in 42.2% of women in the study, 16.6% with reflex possible with high-grade squamous intraepithelial lesions (pHSIL) or worse and 54.9% with normal cytology. There were 24.8% of women with positive HPV16/18 who had histological confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 10.3% CIN2+ (including six cancers) among women with reflex negative cytology and 87.7% CIN2+ among women with reflex HSIL cytology. In women with positive HPV (not 16/18), CIN2+ was found in 60.2% with reflex pHSIL or worse cytology (higher risk) and 10.2% with reflex low-grade SIL (LSIL) or normal cytology (intermediate risk). Median waiting time to colposcopy with the intermediate-risk group went up to 181 days. Our colposcopists were able to achieve a positive predictive value (PPV) for CIN2+ of 69.9%, higher than 57.8% PPV in the National Cervical Screening Program (NCSP) 2020 monitoring report. Women with type 3 transformation zone on colposcopy could be followed up with CST if no HSIL was suspected on screening or at colposcopy as their risk of CIN2+ was only 2.5%. CONCLUSIONS: Our findings support direct referral to colposcopy for women with higher-risk CST, with all cancers confined to this group. The NCSP recommendation to refer for colposcopy only after three intermediate-risk CST will need monitoring with the LSIL triage group.

Outcomes of women with positive oncogenic HPV and reflex cytology showing possible high-grade squamous intraepithelial lesion.

AIM: To examine outcomes in women following cervical screening detection of oncogenic human papillomavirus (HPV), with reflex cytology showing possible high-grade squamous intraepithelial lesion (pHSIL). MATERIALS AND METHODS: A retrospective observational study of 523 women seen in the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. RESULTS: Two hundred eighty-two (53.9%) women had histology-confirmed HSIL, encompassing CIN2 or worse (CIN2+), including seven cancers (1.3%) and two adenocarcinoma in situ (AIS) (0.4%). In 81.2% (229/282) of women with CIN2+, this was detected on cervical biopsy at initial colposcopy, with another 8.9% (25/282) of CIN2+ detected at cervical excision following initial colposcopy and the remaining 9.9% (28/282) at follow-up colposcopy thereafter. When discordant cervical biopsy results were discussed at multidisciplinary meeting (MDM), 66.7% of women with pHSIL cytology upgraded to definite HSIL were found to have CIN2+, but only 20.8% when pHSIL cytology was retained and none when downgraded to low-grade (LSIL) or normal. No significant difference was found in the proportion of CIN2+ based on patient age above or below 40, HPV16 and/or 18 versus non 16/18, or whether discordant findings were reviewed at MDM. CONCLUSIONS: We propose a pathway for management of women with positive oncogenic HPV and reflex pHSIL cytology. MDM review is recommended when CIN2+ is not identified on cervical biopsy at initial colposcopy. Conservative management is safe with low risk of CIN2+ when LBC prediction of pHSIL is confirmed or downgraded at MDM with no high-grade change on colposcopy or repeat cytology.

Compliance with follow-up Test of Cure and outcomes after treatment for high-grade cervical intraepithelial neoplasia in Victoria, Australia.

BACKGROUND: Test of Cure (ToC), a combination of testing for oncogenic human papillomavirus (HPV) and cytology, at 12 months post-treatment and annually thereafter, was approved in Australia in 2005 for follow-up of women treated for high-grade squamous intraepithelial lesions (HSIL) of the cervix. AIMS: To determine among women resident in Victoria, Australia, the compliance with ToC and the incidence of recurrence up to five years after successful ToC. MATERIALS AND METHODS: A retrospective analysis of women with HSIL (diagnosed at pre-treatment punch biopsy or at excision) who had excisional treatment between 1 January 2007 and 31 December 2011. De-identified data were retrieved from the Victorian Cervical Cytology Registry in Melbourne as at 24 April, 2015. Successful ToC is defined as the occurrence of two consecutive normal (negative) co-tests. Recurrence after treatment is defined by histologically detected HSIL or greater. RESULTS: There were 8478 women who had excisional treatment for HSIL, with 448 (5.5%) experiencing recurrence. Only 2253 (26.6%) women successfully completed ToC, with a decreasing likelihood of ToC completion by time since year of treatment (32.0% in 2007 compared with 20.9% in 2011). Only one (0.08%) woman had HSIL on histology after successful ToC. From the 2007 cohort, 555 (32.0%) women completed ToC successfully and no HSIL recurrence occurred thereafter (median subsequent follow-up period of 4.7 years). CONCLUSIONS: Our study confirmed that women who successfully complete ToC can be returned to five-year routine screening. However, more concerted efforts are needed to ensure that all women treated complete ToC.

Recurrent post-coital bleeding: Should colposcopy still be mandatory?

BACKGROUND: Colposcopy has been recommended for all women with recurrent post-coital bleeding (PCB) even if their cervical cytology or co-test (involving oncogenic human papillomavirus (HPV) DNA testing and cytology) are negative. AIMS: To determine the risk of cervical cancer and its precursors among women with recurrent PCB with negative cytology or co-test. MATERIALS AND METHODS: A retrospective analysis of two cohorts of women with PCB referred to a tertiary colposcopy clinic. Cohort (1) (n = 1846) between 1 January 2000 and 31 December 2016 (cytology-based screening) and Cohort (2) (n = 215) from 1 January 2018 to 31 December 2019 after introduction of primary HPV screening. RESULTS: In 1217 (65.9%) women in Cohort (1) referred with negative cytology, there was one cancer (0.08%) and 22 high-grade squamous intraepithelial lesions (HSIL (cervical intraepithelial neoplasia 2/3)) on histopathology. In Cohort (2), there was no cancer or HSIL in 83 women with negative co-tests (negative for oncogenic HPV and cytology). False-negative cytology after a negative referral cytology or co-test was low with 2% of repeat cytology at initial colposcopy showing possible HSIL or worse. CONCLUSIONS: Women presenting with PCB and negative cytology alone have a low risk of cancer and could have HPV testing before being triaged to colposcopy. We showed that with the assurance of a negative co-test and the low likelihood of false-negative cytology, these women could avoid colposcopy unless cervical cancer is clinically suspected. There is a need for a larger cohort study to substantiate our findings with more precision.

Management and long-term outcomes of women with adenocarcinoma in situ of the cervix: A retrospective study.

BACKGROUND: Adenocarcinoma in situ of cervix is increasingly managed by local excision rather than hysterectomy and this study will ascertain if conservative management by excision alone is adequate. AIMS: To evaluate the long-term outcomes of conservative management of adenocarcinoma in situ of cervix, particularly in relation to excisional margin status. MATERIALS AND METHODS: Retrospective analysis of women diagnosed with adenocarcinoma in situ and their management between 1992 and 2010 retrieved from the Victorian Cervical Cytology Registry, Australia. Failure of conservative treatment is defined by histologically proven adenocarcinoma in situ or adenocarcinoma at follow-up after negative excisional margins. RESULTS: adenocarcinoma in situ of the cervix was managed primarily with cold knife cone biopsy or loop electrosurgical excision of the cervix. Most excisions were in one piece (83.4%) with average depth of 16.1 mm and 21.9% had involved excisional margins. Women with adenocarcinoma in situ on any excisional margin were more likely to have residual or recurrent disease (28.7%) compared with negative excisional margins (4.3%). Residual adenocarcinoma in situ was twice as common if adenocarcinoma in situ was present at endocervical (29.6%) and stromal (23.1%) margins compared with an ectocervical margin (13.6%). Cancer incidence at follow-up was 2.3% for women with positive excisional margins compared to 1.3% with negative margins. CONCLUSIONS: Women with adenocarcinoma in situ of cervix can be managed with local excisional procedures, best in single pieces to provide the important information on excisional margins. Adenocarcinoma in situ at endocervical and stromal excisional margins needs re-excision or where appropriate, hysterectomy, while negative excisional margins have a low rate of recurrence and can be followed up with test of cure.

Findings and Outcomes in a Prevaccination Cohort of Women Younger Than 25 Years Attending a Tertiary Colposcopy Service.

OBJECTIVE: To describe clinical presentation and treatment in women younger than 25 years referred to the Royal Women's Hospital colposcopy clinic, before implementation of the National Human Papillomavirus Vaccination Program. METHODS: Retrospective cohort analysis of women younger than 25 years referred to a tertiary hospital colposcopy clinic between 1998 and 2007. Clinical presentation and correlation between cervical cytology, biopsy, and histology at treatment was examined. RESULTS: Approximately 14,635 colposcopies were undertaken in 4104 women (median age, 22 years); 3051 had abnormal referral cytology, of whom, 23.8% had high-grade disease on punch biopsy. High-grade disease was found in 15.1% of those with possible low-grade or low-grade cytology (293/1932), 42.4% of those with possible high-grade or high-grade cytology (474/1119). Sensitivity and specificity of colposcopy for high-grade disease (high-grade epithelial abnormality, adenocarcinoma in situ, cervical cancer up to 2 years follow-up) was 60.0% and 82.3%, respectively. Thirty-nine percent (n = 1180) with abnormal cytology had treatment, of which, 66.6% was ablative. Histological CIN3+ was found in 53.8% of those with a previous high-grade punch biopsy (126/234) at excisional treatment, and 23.0% of those with a previous low-grade punch biopsy (20/87) (relative risk, 2.3 [CI, 1.6-3.5]). Four cancers were detected (0.1% of the total cohort, 0.5% of those with a high-grade biopsy, and 1.7% of those with a high-grade biopsy who underwent excisional treatment.) CONCLUSIONS: Before vaccination, young women experienced a high real-time burden of high-grade disease and high rates of intervention. These baseline data contribute to monitoring of HPV vaccination and revised cervical screening strategies.

Hybrid Capture II testing for high-risk human papillomavirus DNA in the follow-up of women treated for high-grade cervical intraepithelial neoplasia.

OBJECTIVE: This study aimed to estimate and compare the validity of high-risk human papillomavirus DNA (HR-HPV DNA) testing using Hybrid Capture II with and without Pap cytological examination in the detection of incident high-grade cervical intraepithelial neoplasia (CIN 2+) after treatment. MATERIALS AND METHODS: A total of 1,608 women undergoing ablative or excisional treatment were recruited to the study between May 2001 and June 2005, of whom 985 women were treated for CIN 2+. High-risk HPV DNA tests and Pap smears were performed once in every 6 months for 24 months after treatment. RESULTS: A total of 888 women were eligible for analysis. High-grade cervical intraepithelial neoplasia was detected in 22 women (2.5%) for the 24 months after treatment. The sensitivity for CIN 2+ detection with cytological diagnosis ranged from 43% to 100%, from 67% to 100% for HR-HPV DNA test, and from 67% to 100% for both tests combined. The specificity of cytological diagnosis ranged from 94% to 97%, from 75% to 84% for HR-HPV DNA test, and from 80% to 82% for both tests combined. The positive predictive value for cytological diagnosis ranged from 8% to 30%, from 4% to 14% for HR-HPV DNA test, and from 4% to 11% for both tests combined. The negative predictive value was 99% or greater for cytological diagnosis alone, HR-HPV DNA test alone, or for both tests combined. CONCLUSIONS: As histologically proven CIN 2+ after treatment for this group of women was low, adding HR-HPV DNA testing to Pap smear did not increase the detection of CIN 2+ or enhance the negative predictive value of cytological diagnosis alone.

Cervical Cancer Working Group report.

Disease burden of cervical cancer in Asia was summarized. Human papillomavirus 16 is the most oncogenic human papillomavirus type. Korea's national cervical cancer screening program targets women aged 30 or over, with coverage of almost 80%. Japan has a long history (50 years) of cervical cancer screening, and cytological screening programs have reduced the incidence/mortality of cervical cancer by 70%. But, recent cervical cancer screening coverage is ∼24%. Modeling suggested that vaccination of all 12-year-old girls would reduce cervical cancer cases by 73% in Japan. India has no cervical cancer screening program, as well as a serious lack of awareness in the general population, medical professionals and policy-makers. A realistic, affordable approach would be a low-volume, once-in-a-lifetime human papillomavirus-based screening program. In Australia, the national cervical cancer program has been very successful in reducing the incidence and mortality of cervical cancer. Australia was the first country to implement free, national human papillomavirus immunization (April 2007), expected to reduce human papillomavirus 16 infections by 56% in 2010 and 92% in 2050. A comparison of the UK and Japan was demonstrated that in the UK, cervical cancer screening and human papillomavirus vaccination uptakes are high because the government provides adequate education/funding. The Japanese government needs to put more emphasis on women's health and preventative medicine. Our conclusion and recommendations are that heightened public awareness of cervical cancer prevention, focusing on screening and vaccination will lead to improved survival and a better quality of life.

New technologies and advances in colposcopic assessment.

To have a good grasp of clinical colposcopy, it is necessary to understand the histopathologic structure of the normal and dysplastic cervical epithelium. Previous meta-analyses had indicated high overall sensitivity of colposcopy in detecting dysplastic lesions, but recent studies have suggested that the technique has much lower sensitivity in detecting high-grade intraepithelial neoplasia. The best practice in colposcopy relies on accurately taking a biopsy from the correct (i.e. most morphological abnormal) site, and by taking more than one biopsy, the sensitivity for detection of high-grade cervical intraepithelial neoplasia can be increased. Cytological screening programmes of proven and maintained high quality will enhance the predictive colposcopic accuracy for high-grade cervical intraepithelial neoplasia after referral. With the advent of computerised colposcopy and the Internet, digital imaging can be transmitted in real-time for instant viewing, facilitating distant consultation and education. This form of 'telemedicine' will allow family practice and remote areas to have access to colposcopy expertise. Of all the currently available technological adjuncts to colposcopy, spectroscopy devices have demonstrated relatively high sensitivities, and seem to have the best potential to become the technique of choice in future routine clinical practice in developed countries following the human papillomavirus vaccination. Other alternatives may need to be used in parts of the globe with high disease incidence and without organised screening or vaccination programmes. Opportunities remain for global collaboration in research, education and training to promote more effective and affordable cervical screening, and to enhance the skills of colposcopists worldwide.