An analysis of “long-term” follow-up results in patients with cervical intraepithelial neoplasia treated by cryotherapy

Richart, Ralph M.; Townsend, Duane E.; Crisp, William E.; DePetrillo, A.D.; Ferenczy, Alex; Johnson, Gary R.; Lickrish, Gordon M.; Roy, Michel; Santa, Umberto Villa

doi:10.1016/0002-9378(80)90892-3

Cited by 95 publications

(19 citation statements)

References 3 publications

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“…An intriguing observation was the loss of the SC junction immunophenotype following excision. There is a high cure rate for CIN following successful excision or ablation of the SC junction (20,21). Cure is usually attributed to the combination of removing the preinvasive neoplasm and a secondary immune system that prevents reinfection by HPV.…”

Section: Discussionmentioning

confidence: 99%

A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer

Herfs

Yamamoto

Laury

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

371

280

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Infection by carcinogenic human papillomaviruses (HPV) results in precancers [cervical intraepithelial neoplasia (CIN)] and cancers near the ectoendocervical squamocolumnar (SC) junction of the cervix. However, the specific cells targeted by HPV have not been identified and the cellular origin of cervical cancer remains elusive. In this study, we uncovered a discrete population of SC junctional cells with unique morphology and gene-expression profile. We also demonstrated that the selected junctional biomarkers were expressed by a high percentage of high-grade CIN and cervical cancers associated with carcinogenic HPVs but rarely in ectocervical/transformation zone CINs or those associated with noncarcinogenic HPVs. That the original SC junction immunophenotype was not regenerated at new SC junctions following excision, not induced by expression of viral oncoproteins in foreskin keratinocytes, and not seen in HPV-related precursors of the vagina, vulva, and penis further support the notion that junctional cells are the source of cervical cancer. Taken together, our findings suggest that carcinogenic HPV-related CINs and cervical cancers are linked to a small, discrete cell population that localizes to the SC junction of the cervix, expresses a unique gene expression signature, and is not regenerated after excision. The findings in this study uncover a potential target for cervical cancer prevention, provide insight into the risk assessment of cervical lesions, and establish a model for elucidating the pathway to cervical cancer following carcinogenic HPV infection.

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Section: Discussionmentioning

confidence: 99%

A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer

Herfs

Yamamoto

Laury

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

371

280

View full text Add to dashboard Cite

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“…In case 6 colposcopic biopsy showed cervical intraepithelial neoplasia III, and two further severely dyskaryotic smears from the clinic preceded the diagnosis of carcinoma 10 months later. 8,9, and 10) occurred among the 434 patients who were lost to follow up. All three patients had had only one mildly dyskaryotic smear and were found to have invasive cancer two, six, and 12 years later.…”

Section: Invasive Cancersmentioning

confidence: 99%

Risk of cervical cancer associated with mild dyskaryosis.

Robertson

Woodend

Crozier

et al. 1988

BMJ

138

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“…A fundamental local immunological defect could increase the risk of acquiring HPV-related diseases in a portion of the sexually active population. That an immune response occurs locally, however, is supported by the fact that successfully treated women have a low risk of new disease, presumably because of some protective immunological function [34]. Alternatively, potentially oncogenic viruses may escape immune surveillance for a long enough period to produce an immortal cell population that is no longer dependent upon replicating virus.…”

Section: The Local Immune Response To Genital Papiilomavirusmentioning

confidence: 95%

Local immunity and the uterine cervix: Implications for cancer-associated viruses

Roche

Crum

1991

Cancer Immunol Immunother

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Studies of cervical secretions as well as cells composing the endocervix have provided evidence for a functional and potentially important immunological system in the mucosa of that organ. The availability of the tools of cell biology as well as three agents that may be used as probes to infect cervical mucosa experimentally has made possible a detailed approach to define the structural and functional characteristics of local cervical immunity. A long-term goal of these studies is to determine how the cervical immune response may be regulated to reduce local viral replication and virus-associated diseases. With Langerhans cells for antigen presentation, cervical immune responses generally remain detectable for more than 30 days, are predominantly of the IgA isotype, can be influenced by estrogen or progesterone, and are best elicited by local rather than systemic exposure to antigen. Cervical immune responses to the human papillomaviruses (HPV) are of particular importance in this regard because this virus is associated with cervical neoplasia. While responses in serum to HPV-16 proteins L1, E4, and E7 has been found in up to 78% of persons with HPV-associated cervical neoplasms, data showing that a local response of comparable frequency consistently occurs have yet to be confirmed. The current status of local HPV-16-specific immunoglobulin as a potentially useful indicator of HPV-16-related infection or pre-cancer is controversial, and is confounded by several potentially important factors, including patient age, estrogen/progesterone level, smoking status, and sample admixture with serum immunoglobulin.

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An analysis of “long-term” follow-up results in patients with cervical intraepithelial neoplasia treated by cryotherapy

Cited by 95 publications

References 3 publications

A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer

A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer

Risk of cervical cancer associated with mild dyskaryosis.

Local immunity and the uterine cervix: Implications for cancer-associated viruses

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