Unique recurrence patterns of cervical intraepithelial neoplasia after excision of the squamocolumnar junction

Abstract

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamocolumnar junction (SCJ) and suggest that these cells may not regenerate after excision (loop electrosurgical excision procedure). Our study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (human papillomavirus, HPV) characteristics of recurrent CIN. One hundred and thirty-one consecutive patients treated by excision and attending follow-up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype and SCJ immunophenotype. During the follow-up period (up to 4 years), 16 (12.2%) recurrences were identified. Four (25%) were identified at the first follow-up visit, closely resembled the initial CIN 2/3 in grade and HPV type and were typically SCJ marker positive [SCJ(1)], suggesting nonexcised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (2). In total, 9 out of 11 SCJ (2) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This markedly lower risk of CIN 2/3 after successful SCJ excision suggests that the removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer.Human papillomavirus (HPV) has been linked to cervical cancer and its precursors from the early 1980s.1,2 To date, more than 100 HPV genotypes have been characterized and vaccination programs of sexually naive individuals are anticipated to eventually achieve a significant reduction in cervical cancer incidence and mortality. 3,4 Despite this, there is a large population of women in both high-and low-resource settings, who have been exposed to HPV and will be at risk for cervical cancer irrespective of vaccination. Management of this subset of women remains within the realm of conventional screening and HPV testing with the removal of potentially dangerous precancers (cervical intraepithelial neoplasia or CIN 2/3) by cryoablation or excision (loop electrosurgical excision procedure [LEEP] or cone biopsy). Protocols using a pre-emptive "see and treat" strategy are being explored in low-resource settings and are designed to identify the candidate CIN by the application of acetic acid to the cervix followed by immediate ablation/excision of the acetowhite areas.Ablation/excision techniques are highly successful in both removing CIN 2/3 and preventing recurrence, achieving an approximately 90% cure rate with a very low risk of a cervical cancer outcome. 5,6 This high success rate has been generally credited to both the removal of the lesion and an acquired HPV type-specific immune response that protects the cervical ...

The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador

“…28 Also, speculatively, the ablation of the squamocolumnar junction may reduce future risk of acquiring a new HPV infection that could progress to cancer. 29 We note that, due to the low specificity of local pathology diagnoses, most women in the CM cohort who received colposcopy were referred to treatment; thus, the potential for overtreatment exists with both management strategies. While we included economic costs of routine follow-up visits after cryotherapy and LEEP, we did not include additional costs or health consequences associated with major adverse events resulting from treatment, due to limited data on these rare outcomes in Phase I.…”

Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women

“…64-66 The squamocolumnar junctions are thought to be the cells initially infected by HPV and thus give rise to clinically significant precursor lesions and carcinoma; by ablating this region, the potential to develop lesions is drastically reduced, regardless of the HPV type present. 67-69 However, the feasibility, safety, and efficacy of this approach have yet to be proven.…”

Deciphering the Multifactorial Susceptibility of Mucosal Junction Cells to HPV Infection and Related Carcinogenesis

“…The discovery of SC junction cells might point the way to a different, low-cost, and simple way to prevent cervical cancer in underserved populations: by removing the vulnerable cells that are its source. This recently-proposed clinical perspective is supported by historical data [78,79,80]. Over 50 years ago, Paul Younge (Boston Lying-in Hospital) routinely cauterized the uterine cervices of his patients postpartum.…”