Pathogenesis (development of disease)
Cervical carcinoma usually originates from cervical intraepithelial neoplasia (CIN). This usually originates at the external cervix. In over 90% of cases, the cell changes begin in the transformation zone of the cervix between the squamous and cylindrical epithelium. The transition from a CIN1 to a cervical carcinoma is much less likely, in contrast to a CIN III. A CIN I progresses to severe dysplasia (CIN3/carcinoma in situ) in only 11% or to invasive carcinoma in 1% if left untreated. In contrast, CIN III progresses to invasive carcinoma in 30-70% of cases in a time-dependent manner, but can still regress spontaneously in 32% of cases.
Intermediate grade cervical intraepithelial neoplasia (CIN 2) shows the following course: After two years, half (50%) of the lesions had spontaneously regressed, one-third (32%) had not changed, and progression to a CIN 3 lesion or carcinoma had occurred in just under one-fifth (18%). Based on these results, the authors believe that “active surveillance” is warranted for CIN-2 lesions.
The reason for the changes in cells is HPV infection with high-risk papillomaviruses (mainly HPV types 16, 18).
Note: Not all cervical carcinomas are caused by HPV. In 8 of 178 primary tumors examined, genomic analysis of the tumor found no evidence of infection with HPV and its oncogenes such as E6 and E7 (= HPV-negative carcinomas). Seven of the eight carcinomas showed high similarity to endometrial carcinoma (uterine cancer), i.e., they also differed in other genes.
Etiology (causes)
Biographic causes
- Genetic burden from parents, grandparents
- Genetic risk depending on gene polymorphisms:
- Genes/SNPs (single nucleotide polymorphism):
- Genes: IL21A, IL21B
- SNP: rs568408 in the gene IL21A
- Allele constellation: AG (1.43-fold).
- Allele constellation: AA (2.0-fold)
- SNP: rs3212227 in the IL21B gene.
- Allele constellation: AC (1.43-fold).
- Allele constellation: CC (2.0-fold)
- Genes/SNPs (single nucleotide polymorphism):
- Genetic risk depending on gene polymorphisms:
- Socioeconomic factors – low socioeconomic status.
- Multiparity/high parity (number of births).
Behavioral causes
- Nutrition
- Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
- Consumption of stimulants
- High promiscuity or sexual contacts with promiscuous partners.
- Poor genital hygiene
Causes related to disease
- Infection with human papillomaviruses HPV-6, 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73, 82 (consistent use of condoms reduces the risk of transmission of HPV infection) N.B.: HPV vaccination against the two most common high-risk HPV types 16 and 18 can prevent circa 70% of cervical cancers!
- Early and frequent viral genital infections, especially with the herpes simplex virus (HSV), or the HI virus (HIV).
- Immunodeficiency
Medication
- Immunosuppression
- Immunosuppressants: azathioprine – highest risk was 5 years after high-dose therapy at the earliest (hazard risk 3.3; 95% CI 1.5-7.1)
- Long-term use of oral contraceptives (“the pill”).
Other causes
- Positive HPV test (especially in women over 30) – increased risk of cervical dysplasia (cervical intraepithelial neoplasia/CIN).
- Prostitution