Introduction

Adenocarcinoma in situ (AIS) of the cervix is a precursor to invasive adenocarcinoma but behaves differently from squamous precancer. Its endocervical location, multifocality, and potential for skip lesions make detection and complete excision challenging. AIS is human papillomavirus (HPV) related and may coexist with squamous dysplasia. It is most strongly associated with high-risk HPV types 18 and 16, with smaller contributions from other oncogenic types such as HPV 45 and is more likely to evade cytological detection.¹

These features underpin the ongoing relevance of glandular disease despite the success of cytology-based screening in reducing squamous pathology. As Australia moves toward cervical cancer elimination, AIS is a lesion that is less visible, less predictable, and often complex to manage.

Primary HPV screening has improved detection of oncogenic HPV types linked to glandular disease, and HPV vaccination has reduced high-grade precancer at a population level.^2,3 However, AIS continues to warrant attention due to its association with occult invasive disease and complex natural history.^1,4 Multi-focal disease occurs in up to 15% of cases. This leads to risks of recurrence even with negative margins necessitating a different post-treatment follow-up to squamous related dysplasia.⁵

Although the relative increase in cervical adenocarcinoma reflects reduced squamous cell carcinoma incidence, it also highlights limitations of cytology for detection of glandular lesions arising higher in the endocervical canal.² Despite advances in screening and prevention, AIS remains clinically significant, particularly in guiding decisions around excision, fertility preservation, and long-term surveillance.

Diagnosis – Maintaining a High Index of Suspicion

AIS is most often identified following a positive high-risk HPV test with cytological abnormalities such as atypical glandular cells. However, both cytology and colposcopy have limitations.¹ Colposcopy findings are often subtle or absent, and disease may extend beyond the transformation zone. Hence, diagnosis frequently relies on excisional procedures rather than directed biopsy alone.⁶

All patients with a confirmed AIS require excisional treatment, regardless of biopsy findings.  Excision serves to confirm the diagnosis and exclude invasive disease. Cold knife conisation (CKC) is often preferred due to more accurate margin assessment and reduced thermal artefact.¹ Excision depth should be age-guided: <35 years, 15 mm; ³35 years, 15–25 mm, reflecting increased likelihood of lesions extending beyond the transformation zone in older patients.^7,8

Accurate diagnosis depends on expert histopathological assessment, as AIS can mimic benign conditions such as tuboendometrioid metaplasia, endocervical glandular hyperplasia, and reactive changes.⁹ Misclassification has significant clinical consequences, supporting subspecialist gynaecological pathology review.

Stratified mucin-producing intraepithelial lesion (SMILE) should also be recognised within the glandular neoplastic spectrum. It shares features with both AIS and high-grade squamous lesions, is HPV related, and may co-exist with AIS, influencing management.¹⁰

Management – Margins Over Method

The key determinant of outcome in AIS is complete excision, rather than technique.⁴ Margin status is the strongest predictor of persistence or recurrence, with positive margins conferring more than threefold increased risk.⁶ However, negative margins do not exclude residual disease, due to skip lesions.^4,6

Management is guided by three questions:

1. Has invasion been excluded (co-existent invasion in up to 15%)?¹
2. Are the margins clear?
3. Is fertility preservation desired?

While CKC remains the traditional standard, loop electrosurgical excision (LLETZ/LEEP) is used in selected patients – those with a fully visible transformation zone, fertility preservation needs, and where an adequate, unfragmented excision of sufficient depth (Type 3) can be achieved. Although associated with higher rates of positive margin rates, outcomes are comparable when margins are clear.^6,11

Current Australian and New Zealand guidelines do not support routine complete hysterectomy. It may be considered where surveillance is not feasible (e.g. cervical stenosis, absent cervical os) or where patient anxiety significantly impacts management.¹²

Fertility-sparing Management and Obstetric Considerations

Fertility-sparing management is increasingly relevant, as AIS is often diagnosed in younger women. Conservative management after excision with clear margins is acceptable in selected patients. Those with involved margins should undergo further excision before considering conservative management, ideally following MDT discussion.

Endocervical curettage (ECC) may assist in assessing residual disease, although sensitivity is limited.¹³ Retrospective and cohort data demonstrate favourable outcomes with structured long-term follow-up.^14,15 Patients should be counselled regarding recurrence risk, surveillance requirements, and the potential need for definitive surgery.

Beyond Oncology – Obstetric Implications

Conisation is associated with an increased risk of preterm birth. Risk factors include greater excision depth, short cervical length, and prior preterm birth. These should be discussed when considering fertility-sparing treatment.¹⁶

Surveillance and Recent Guideline Updates

Persistent HPV positivity is a key predictor of recurrence.¹⁷ This underpins risk-based follow-up in the updated Australian National Cervical Screening Program (NCSP), implemented in April 2025:

• Annual co-testing for five years.
• Three-yearly co-test thereafter if negative.
• Return to routine screening after 25 years of negative surveillance.

Clinician-collected co-testing is required, as self-collected HPV testing does not allow cytology.¹²

Conclusion

AIS remains clinically significant despite advances in vaccination and screening. It continues to present challenges in diagnosis, management, and follow-up.

Key priorities are ensuring complete excision, careful interpretation of margins, individualising management for fertility goals, and maintaining long-term surveillance.