From Infection to Intervention: HPV-Cervical Cancer Timeline

Most HPV infections do not lead to cervical cancer, and the majority of infections resolve on their own without causing long-term harm. Persistent infection with high-risk HPV types is a key factor in the development of cervical cancer. Here are some general timelines and factors to consider.

Timeline

The progression from persistent infection to the development of precancerous lesions (such as cervical dysplasia or cervical intraepithelial neoplasia, CIN) can take several years: from 10 to 15 years on average.

Stage 0: Screening & Detection

Many HPV infections clear on their own within a couple of years, and the immune system is often able to eliminate the virus..

Year 0-2: Stage 1: LSIL / CIN1

Represents mild dysplasia, indicating slight abnormalities in the cells of the cervix.
The changes are often considered low-grade and may resolve on their own without intervention.

Year 3-6: Stage 2: HSIL / CIN2

Indicates moderate dysplasia, signifying more significant abnormalities in the cervical cells. The changes are considered moderate-grade and have a higher likelihood of persisting or progressing if left untreated..

Year 7-10: Stage 3: HSIL / CIN3

Represents severe dysplasia or carcinoma in situ, indicating a high degree of abnormality in the cervical cells. These changes are considered high-grade and have a greater risk of progressing to invasive cervical cancer if not treated.

Year 10-15: Stage 4: Cancer

If left untreated, cervical precancerous lesions may progress to invasive cervical cancer over an extended period.

What is Cervical Dysplasia?


Precancerous Lesions (Dysplasia): Persistent HPV infection can cause changes in cervical cells known as precancerous lesions or dysplasia. These injuries are divided into grades according to severity: mild, moderate and severe. Not all precancerous lesions progress to cancer, and some may return spontaneously.

Can you feel cervical dysplasia?

No. Cervical dysplasia doesn’t cause symptoms, although sometimes you may notice vaginal spotting. Abnormal cells found during a Pap smear are often the first sign of the condition.

Can cervical dysplasia go away?

Mild dysplasia (LSIL or CIN I) may go away without treatment. Changes due to HPV infection may also go away without treatment or dysplasia. You may only need careful follow-up by your provider with repeat Pap tests every 6 to 12 months. If the changes do not go away or get worse, treatment is needed.

How fast does dysplasia turn into cancer?

But if they aren’t treated, there is a chance that these abnormal changes may become cervical cancer. If left untreated, it may take 10 years or more for precancerous conditions of the cervix to turn into cervical cancer, but in rare cases this can happen in less time.

Invasive Cancer: In some cases, precancerous lesions can progress to invasive cervical cancer. This implies that cancer cells have grown beyond the surface layer of the cervix and can spread to other parts of the body.

How often does dysplasia turn into cancer?

With low-grade cervical dysplasia, classified as CIN 1, you likely won’t need treatment. In the majority of these cases, the condition goes away on its own. Only about 1% of cases progress to cervical cancer.

What are the symptoms of Stage 1 cervical cancer?

Vaginal bleeding after intercourse, between periods or after menopause. Menstrual bleeding that is heavier and lasts longer than usual. Watery, bloody vaginal discharge that may be heavy and have a foul odor. Pelvic pain or pain during intercourse

Why in Cervix?

Source: Wikipedia

The terms “cervix” and “cervix uteri” essentially refer to the same anatomical structure within the female reproductive system. Both terms are commonly used interchangeably and describe the lower, narrow portion of the uterus that connects it to the vagina.

Human Papillomavirus (HPV) infections often start in the cervix due to the specific anatomy and characteristics of this area in the female reproductive system. Here are a few key reasons why HPV infections commonly initiate in the cervix:

Exposed Tissues: The cervix contains exposed epithelial tissues, especially on the transformation zone. This area is susceptible to HPV infection. The transformation zone is a region where the squamous epithelium of the vagina transitions into the columnar epithelium of the uterus, making it more vulnerable to viral exposure.

Site of Infection: HPV is primarily a sexually transmitted infection, and the cervix is a common site for sexual contact. During sexual activity, the virus can be transmitted from an infected partner to the cervix, leading to infection.

Vulnerable Cells: The cells in the cervix are susceptible to HPV infection because they are actively dividing and changing, particularly during the menstrual cycle and pregnancy. HPV tends to infect rapidly dividing cells, and the cervix provides an environment conducive to viral replication.

Access to the Uterus: The cervix is the gateway to the uterus. If HPV infection is established in the cervix, it can potentially spread to other parts of the reproductive system, including the uterus.

Viral Persistence: The cervix is exposed to various factors, and HPV has the ability to persist in the epithelial cells. Persistent infection with high-risk HPV types is a significant risk factor for the development of cervical cancer.

Cervix divisions

The cervix is a small round organ, with an opening called the os. 

The cervix forms a canal, which joins the top of the vagina to the lower part of the womb. This is called the endocervical canal. 

The cervix is divided into the: 

  • ectocervix – the outer surface of the cervix. 
  • endocervix – the inside of the cervix.

The types of cells that form the cervix are: 

  • squamous cells – flat, thin cells that look like skin and cover the outer surface of the cervix 
  • glandular cells – cells shaped like columns that make a fluid called mucus and cover the inside of the cervix. 

The transformation zone is the area where glandular cells and squamous cells meet. It is found around the opening of the cervix. 

The transformation zone is where the nurse or doctor will take a sample of cervical cells from during cervical screening (a smear test).

Glandular cells in the cervix make a fluid called mucus. The mucus is usually clear or white and there may be more of it at different times in the menstrual cycle. It is sometimes called cervical discharge.

This mucus keeps the cervix, womb, ovaries and fallopian tubes healthy by helping protect them from bacteria that could cause infection. 

Cell changes

Sometimes, our cells act in ways they shouldn’t and become abnormal. We call this a ‘change’.  Depending on where cell changes are, they may be called cervical intraepithelial neoplasia (CIN) or cervical glandular intraepithelial neoplasia (CGIN), and SMILE.

CIN

CIN stands for cervical intraepithelial neoplasia. CIN is named after the parts of the cervix it affects, which are the squamous cells on the outer surface. It is the most common type of cell changes.

CIN is graded:

  • CIN1
  • CIN2
  • CIN3
CGIN / AIS

CGIN stands for cervical glandular intraepithelial neoplasia. CGIN is named after the parts of the cervix it affects, which are the glandular cells inside the cervical canal. 

Adenocarcinoma in situ (AIS) is another name for CGIN. 

CGIN is graded:

  • Low grade
  • High grade
SMILE

CIN is the most common type of cell changes, with CGIN being the second most common. But there are other types of cell changes you can have, including SMILE.

SMILE stands for stratified mucin-producing intraepithelial lesion. It is thought of and treated in a similar way to CGIN. However, it is much rarer.

With the right management, the risk of cell changes developing into cervical cancer is low. Most cell changes do not develop into cervical cancer. Sometimes people use the words ‘precancerous cells’ when talking about CIN or CGIN. This does not mean CIN or CGIN will definitely develop into cervical cancer. It just means that the cells are abnormal, but are not cancer cells.

Most people with cell changes will not develop a HPV-related cancer. However, having cell changes is linked to an increased risk of developing cervical cancer and other HPV-related cancers, such as vulval, vaginal and anal cancer. But even with an increased risk, the likelihood of developing one of these cancers is low. 

Soure: Research Gate

The progression of cervical cells to cervical cancer generally follows a gradual process that involves changes in the DNA of the cervical cells.

This process is known as cervical carcinogenesis and usually takes many years.

Virus types that cause cervical dysplasia


Certain strains of HPV can cause changes in the cells of your cervix, a condition called cervical dysplasia. If left untreated, cervical dysplasia sometimes progresses to cervical cancer

  • HPV-16: It is estimated that HPV-16 is present in approximately 50% of all cervical cancer cases.
  • HPV-18: It is found in about 20% of cervical cancer cases.
  • In addition to these two types, there are other high-risk types of HPV that can also contribute to the development of cervical cancer, although to a lesser extent. Some of these include HPV-31, HPV-33, HPV-45, among others.

High-risk forms of HPV often do not cause symptoms until they turn into cancer. Cervical cancer is the most common type of HPV-related cancer. Other types of cancer are much rarer. They include:

  • Anal cancer. Penile cancer. Throat cancer. Vaginal cancer. Vulvar cancer.
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