Cervical cancer
Cervical Cancer
Epidemiology:
Cervical cancer, primarily driven by persistent infection with high-risk human papillomaviruses (HPVs), is one of the leading causes of cancer-related mortality among women globally, with approximately 604,000 new cases reported 1. Spontaneous remission (SR) in cervical cancer is exceedingly rare, with documented cases constituting less than 1% of all cervical cancer incidents 2. Instances of SR typically involve the regression of cervical intraepithelial neoplasia (CIN), with studies indicating that a notable proportion of low-grade lesions may resolve spontaneously; however, this phenomenon is not well understood within the context of invasive cervical cancer 3. The challenge in estimating the true frequency of SR in cervical cancer lies in the often subtle and unrecognized nature of these events, necessitating further research into the immunological and environmental factors that may promote such unexpected clinical outcomes 4.
Clinical Characteristics:
To date, there have been four reported cases of SR involving either primary or metastatic carcinoma of the cervix. The patients’ ages at the time of regression ranged from 36 to 54 years, with all reported cases occurring in females, consistent with the disease’s gender distribution. See Table 1 below for further information.
Histological Characteristics:
Of the cases analyzed, the histology of the tumors was primarily reported as adenocarcinoma of the cervix, with varying degrees of differentiation among the cases. Instances of non-epithelial malignancies, such as lymphomas or other gynecologic tumor types, were excluded from this data collection to maintain diagnostic consistency.
Proposed Contributing Mechanisms:
Among the reported cases, therapeutic interventions varied considerably. One patient achieved remission following the use of herbal treatment, while another exhibited remission after insulin-induced hypoglycemic therapy administered for psychiatric purposes. In one case, immunomodulation was suggested as a contributing factor, with long-term remission sustained over a decade. Another report attributed tumor regression to biopsy-induced trauma, implying an immune-mediated response following mechanical disturbance of the lesion. Collectively, these findings highlight that immune activation, metabolic disturbance, and physical intervention may play contributory roles in spontaneous remission of cervical carcinoma.
Site and Extent of Remission:
Among the reported cases, complete tumor regression was observed in the majority of patients, with both primary and metastatic lesions demonstrating resolution in several instances. Two cases documented remission of the primary cervical tumor, while others showed regression of metastatic sites, including the breast, thorax, pleura, lung, bone, skin, lymph nodes, and abdominal cavity. One patient maintained remission for 10 years, indicating durable disease control. The available follow-up data, though limited, suggest that spontaneous remission in cervical carcinoma may, in select cases, lead to long-term survival, contrasting with the poorer outcomes typically observed in other malignancies where SR is transient or incomplete.
Table 1: Cervical Cancer SR Cases and Clinical Characteristics
Author–year | Age/sex | Primary site | Remission site | Proposed mechanisms | Follow-up |
|---|---|---|---|---|---|
45/F | Cervix | Cervix, Breast, Thorax | Herbal treatment | Not reported | |
53/F | Cervix | Abdominal cavity, Lymph nodes | Insulin-induced hypoglycemia | Not reported | |
36/F | Uterine cervix | Pleura, Lung, Bone, Skin | Immunomodulation | 10 years | |
54/F | Cervix | Cervix, Lymph nodes | Biopsy-induced trauma | Not reported | |
45-year-old Caucasian woman, smoker 45 pack-years, cocaine and heroin, stopped drug abuse a long time ago. History of gastric banding, abdominalominoplasty, and recurrent abscess excision in the breast due to mastitis non-puerperalis. | Lung, Liver, Bladder, Uterus | the patient became asymptomatic, and two months later a follow-up PET-CT showed remarkable partial remission of LCH | the patient became asymptomatic, and two months later a follow-up PET-CT showed remarkable partial remission of LCH | ||
Patient was a nullipara, aged thirty-three, but looked much older. No history of any pelvic inflammation, syphilis, gonorrhea, or tuberculosis. Physical examination showed heart, lungs, kidneys, urine, liver normal; spleen not enlarged; upper abdomen normal. | Instead of growing worse she improved for a time. On June 25, 1903, four and a half years later, she came into my office. She was thin, pale, and weak. The lower abdomen occupied by a hard, irregular mass and above this many hard, irregular, movable bodies of varying size. The vagina filled with a soft, friable, easily bleeding mass, whose base could not be reached, which distended the canal and came down to the perineum. | Instead of growing worse she improved for a time. On June 25, 1903, four and a half years later, she came into my office. She was thin, pale, and weak. The lower abdomen occupied by a hard, irregular mass and above this many hard, irregular, movable bodies of varying size. The vagina filled with a soft, friable, easily bleeding mass, whose base could not be reached, which distended the canal and came down to the perineum. | |||
51-year-old housewife, gravida viii, para vi | Complete disappearance of the shadows, negative Friedman test, no abnormalities on follow-up examinations, x-rays, and Friedman tests | Complete disappearance of the shadows, negative Friedman test, no abnormalities on follow-up examinations, x-rays, and Friedman tests | |||
References:
- Alam M., Ali A., Mehdi S., et al. Hpv typing and its relation with apoptosis in cervical carcinoma from indian population. Tumor Biol.. 2011;33(1):17-22. doi:10.1007/s13277-011-0233-y
- Luhn P., Walker J., Schiffman M., et al. The role of co-factors in the progression from human papillomavirus infection to cervical cancer. Gynecologic Oncology. 2013;128(2):265-270. doi:10.1016/j.ygyno.2012.11.003
- Tainio K., Athanasiou A., Tikkinen K., et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. 2018:k499. doi:10.1136/bmj.k499
- Pedersen K., Fogelberg S., Thamsborg L., et al. An overview of cervical cancer epidemiology and prevention in scandinavia. Acta Obstet Gynecol Scand. 2018;97(7):795-807. doi:10.1111/aogs.13313
- Magaton, I. M., Tzankov, A., Krasniqi, F., Rottenburger, C., Zanetti-Daellenbach, R., Grendelmeier, P., Heinzelmann-Schwarz, V., Mayears, M., & Schwab, F. D. (2017). spontaneous Remission of Severe Systemic Langerhans Cell Histiocytosis with Bladder Involvement: A Case Study. Case reports in oncology, 10(3), 876–884. https://doi.org/10.1159/000480696
- Wells, B. H. 1908. Regression and Calcareous Degeneration of Carcinoma. American Journal of Obstetrics and Diseases of Women and Children 57: Mar 1908; 403-406
- Natsume & Takada, 1961. Choriocarcinoma; An Unusual Case Recurring Nine Years After Subtotal Hysterectomy and Followed by Spontaneous Regression of Pulmonary Metastases. American Journal of Obstetrics and Gynecology 82(3): Sept 1961; 654-659
- Kurita, M., Hirano, K., Ebihara, S., Takushima, A., Harii, K., Fujino, T., & Fujioka, Y. (2007). Spontaneous regression of cervical lymph node metastasis in a patient with mesopharyngeal squamous cell carcinoma of the tongue: Possible association between apoptosis and tumor regression. International Journal of Clinical Oncology / Japan Society of Clinical Oncology, 12(6), 448-454. doi:10.1007/s10147-007-0711-9
- Ackermann, S., Gehrsitz, C., Mehlhorn, G., & Beckmann, M. W. (2006). Management and course of histologically verified cervical carcinoma in situ during pregnancy. Acta Obstetricia Et Gynecologica Scandinavica, 85(9), 1134-1137. doi:10.1080/00016340600555926
- Bradbury, J. (2005). High-grade cervical dysplasias: To regress or not to regress? The Lancet Oncology, 6(8), 545.
- Chung, S. M., Son, G. H., Nam, E. J., Kim, Y. H., Kim, Y. T., Park, Y. W., & Kwon, J. Y. (2011). Mode of delivery influences the regression of abnormal cervical cytology. Gynecologic and Obstetric Investigation, 72(4), 234-238. doi:10.1159/000324500
- Hopfl, R., Heim, K., Christensen, N., Zumbach, K., Wieland, U., Volgger, B., . . . Fritsch, P. (2000). Spontaneous regression of CIN and delayed-type hypersensitivity to HPV-16 oncoprotein E7. Lancet, 356(9246), 1985-1986. doi:10.1016/S0140-6736(00)03315-8
- Kadish, A. S., Timmins, P., Wang, Y., Ho, G. Y., Burk, R. D., Ketz, J., . . . Albert Einstein Cervix Dysplasia Clinical Consortium. (2002). Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cell-mediated immune responses to an HPV type 16 E7 peptide. Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, 11(5), 483-488.
- Trimble, C. L., Peng, S., Thoburn, C., Kos, F., & Wu, T. C. (2010). Naturally occurring systemic immune responses to HPV antigens do not predict regression of CIN2/3. Cancer Immunology, Immunotherapy : CII, 59(5), 799-803. doi:10.1007/s00262-009-0806-4
- Koeneman, M. M. 2019. Prognostic factors for spontaneous regression of high-risk human papillomavirus-positive cervical intra-epithelial neoplasia grade 2
- Alam M., Ali A., Mehdi S., et al. Hpv typing and its relation with apoptosis in cervical carcinoma from indian population. Tumor Biol.. 2011;33(1):17-22
- Luhn P., Walker J., Schiffman M., et al. The role of co-factors in the progression from human papillomavirus infection to cervical cancer. Gynecologic Oncology. 2013;128(2):265-270
- tainio. Tainio K., Athanasiou A., Tikkinen K., et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. 2018:k499. do
- Pedersen K., Fogelberg S., Thamsborg L., et al. An overview of cervical cancer epidemiology and prevention in scandinavia. Acta Obstet Gynecol Scand. 2018;97(7):795-807