HPV infection and complications arising after HPV infection

The Human Papilloma Virus (HPV) is a sexually transmitted viral infection transmissible through direct skin-to-skin contact. The HPV virus is responsible for causing multiple epithelial and cervical lesions, as well as the development of cervical cancer. Infection with HPV virus may take the form of skin ulcers or warts which, depending on their course, may be benign or malignant.
People who have multiple sexual partners are at high risk of acquiring the HPV virus. There are over 100 different types of HPV virus. Approximately 30 types of viruses are responsible for infection of the genital tract and the development of cervical lesions.

Currently, HPV infection is one of the main causes of cervical cancer. Worldwide, the prevalence of HPV infection in cervical cancer is nearly 99.7%. In Europe, cervical cancer is the second leading cause of death in women, for women aged 15-44, with nearly 24,000 deaths annually. In Romania, approximately every two hours, a woman is diagnosed with cervical cancer, our country ranking first in the European Union in terms of the mortality rate due to cervical cancer. 

Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. The identification of precancerous lesions is made by cytological screening of cervical cells, called Pap smear (Pap test). If there are insufficient cellular abnormalities described by the result given by this test, they can be more easily identified by other procedures, namely by colposcopy or biopsy.
The Pap smear is routine in order to highlight in a timely manner the presence of changes in cervical cells caused by persistent HPV infection. Changes that occur in the cells of the cervix are called cervical dysplasia.

Based on the appearance and number of abnormal cells found in the structure of the cervix, cervical dysplasia is classified as: mild dysplasia (also called CIN I), moderate dysplasia (also called CIN II) and severe dysplasia (also called CIN III). A second classification is the Bethesda classification, which generally appears on the result of the Pap smear, as follows:
  1. Atypical squamous cells of undetermined significance (or ASC-US), which characterize the presence of a few cells of altered appearance, atypical and which do not meet the criteria for an intraepithelial lesion
  2. Atypical squamous cells that do not exclude a high-grade squamous intraepithelial lesion (or AUC-H)
  3. Low grade squamous intraepithelial lesion (or LSIL) characterizing mild dysplasia and cellular changes that are associated with HPV virus
  4. High-grade squamous intraepithelial lesion (or HSIL), which may progress to cancer
  5. Carcinoma
For more details on the Pap smear, please consult your gynaecologist.
Figure 4. Cellular dysplastic changes in the cervix

Left untreated, HPV infection leads to complications. Common complications that arise after HPV infection include:

  • genital warts,
  • anal warts,
  • ulcers or superinfections due to warts,
  • occurrence of cervical, anal, vulvar, vaginal, head and neck cancer,
  • depression, loss of self-esteem.

The risk of malignant transformation of an injury is greatest in people who have low immunity. When a patient has been diagnosed with HPV infection, there is also a 5 – 20% risk of having other sexually transmitted diseases such as gonorrhoea and/or Chlamydia.

Types of precancerous lesions caused by HPV virus

The precancerous lesions of the cervix develop from the epithelium (mucosa) that covers the cervix.

Pre-cancerous changes in the cervix do not usually cause pain or other symptoms. Thus, they are only detected during screening by the Pap smear. Symptoms generally do not appear until the abnormal cervical cells become cancerous and invade nearby tissue. The most common symptoms are foul-smelling profuse vaginal discharge, abnormal bleeding or intermenstrual bleeding, bleeding during or after sexual intercourse, postmenopausal bleeding or back pain.

Pre-cancerous lesions of the cervix are divided into two broad categories: squamous intraepithelial lesions (AUC-H, LSIL and HSIL) and adenocarcinoma in situ.

1. Squamous intraepithelial lesions

They develop in the squamous epithelium and are the most common precancerous lesions caused by HPV virus.
Intraepithelial squamous lesions are divided into two broad categories: low squamous intraepithelial lesions (LSIL), which are minor lesions, with no too high risk of progression to cancer, and high squamous intraepithelial lesions (HSIL) considered major lesions, with a high risk of progression to cancer. They may heal between 2 and 5 years of age and have a low risk of becoming malignant.

The diagnosis of high squamous intraepithelial lesions requires specific criteria to be met, namely: cells are smaller in size, respectively cell cytoplasm is more immature than in LSIL. HSIL is associated with a very high risk of progression to invasive cancer, particularly if the infection is with the viral genotypes HPV16 and/or HPV18.

Histological Types of Cervical Cancer

The World Health Organization defines two main histological types of cervical cancer:
Squamous carcinoma (which makes up about 85% of all cases of cervical cancers)
Adenocarcinoma in situ (which makes up about 10-15% of all cervical cancers).

Squamous carcinoma

Squamous cell carcinoma almost always develops amid cervical dysplasia CIN I, II or III. 

2. Adenocarcinoma in situ

Adenocarcinoma in situ is closely related to HPV infection. Viral genotypes HPV16 and/or HPV18 are present in 80% of cases diagnosed with adenocarcinoma in situ. Adenocarcinoma is associated with risk factors such as a single pregnancy or obesity.

The prognosis is quite reserved, the standard treatment involves total hysterectomy or cervical conical excision for patients wishing to become pregnant.

Adenocarcinoma can often evolve into ovarian metastases.

Read more about the benefits of using Cerviron® in the management of cervical lesions.